ID BLA1_KLEPN Reviewed; 286 AA. AC P0AD64; O07941; P14557; P23982; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 1. DT 02-SEP-2026, entry version 103. DE RecName: Full=Beta-lactamase SHV-1 {ECO:0000303|PubMed:2221867}; DE EC=3.5.2.6 {ECO:0000269|PubMed:10231522, ECO:0000269|PubMed:19351161, ECO:0000269|PubMed:22908166, ECO:0000269|PubMed:23252553}; DE AltName: Full=PIT-2 {ECO:0000305|PubMed:2221867}; DE AltName: Full=Sulfhydryl reagent variable 1 {ECO:0000305}; DE Flags: Precursor; GN Name=bla {ECO:0000303|PubMed:2221867}; GN Synonyms=blaSHV-1 {ECO:0000303|PubMed:2221867}, shv1 {ECO:0000305}; OS Klebsiella pneumoniae. OG Plasmid R974. OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Klebsiella; OC Klebsiella pneumoniae complex. OX NCBI_TaxID=573; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC PLASMID=R974 {ECO:0000303|PubMed:2221867}; RX PubMed=2221867; DOI=10.1128/aac.34.8.1577; RA Mercier J., Levesque R.C.; RT "Cloning of SHV-2, OHIO-1, and OXA-6 beta-lactamases and cloning and RT sequencing of SHV-1 beta-lactamase."; RL Antimicrob. Agents Chemother. 34:1577-1583(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=KPAA-1 {ECO:0000303|PubMed:9145849}, KPZU-13 RC {ECO:0000303|PubMed:9145849}, KPZU-8 {ECO:0000303|PubMed:9145849}, and RC KPZU-9 {ECO:0000303|PubMed:9145849}; RX PubMed=9145849; DOI=10.1128/aac.41.5.943; RA Nuesch-Inderbinen M., Kayser F.H., Hachler H.; RT "Survey and molecular genetics of SHV beta-lactamases in Enterobacteriaceae RT in Switzerland: two novel enzymes, SHV-11 and SHV-12."; RL Antimicrob. Agents Chemother. 41:943-949(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RC STRAIN=15571 {ECO:0000303|PubMed:10639363}; RX PubMed=10639363; DOI=10.1128/aac.44.2.362-367.2000; RA Rice L.B., Carias L.L., Hujer A.M., Bonafede M., Hutton R., Hoyen C., RA Bonomo R.A.; RT "High-level expression of chromosomally encoded SHV-1 beta-lactamase and an RT outer membrane protein change confer resistance to ceftazidime and RT piperacillin-tazobactam in a clinical isolate of Klebsiella pneumoniae."; RL Antimicrob. Agents Chemother. 44:362-367(2000). RN [4] RP NOMENCLATURE. RX PubMed=2039479; DOI=10.1042/bj2760269; RA Ambler R.P., Coulson A.F., Frere J.M., Ghuysen J.M., Joris B., Forsman M., RA Levesque R.C., Tiraby G., Waley S.G.; RT "A standard numbering scheme for the class A beta-lactamases."; RL Biochem. J. 276:269-270(1991). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MUTAGENESIS OF ASN-270. RX PubMed=19351161; DOI=10.1021/bi9003292; RA Drawz S.M., Bethel C.R., Hujer K.M., Hurless K.N., Distler A.M., RA Caselli E., Prati F., Bonomo R.A.; RT "The role of a second-shell residue in modifying substrate and inhibitor RT interactions in the SHV beta-lactamase: a study of ambler position RT Asn276."; RL Biochemistry 48:4557-4566(2009). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP TYR-101. RX PubMed=22908166; DOI=10.1128/aac.00711-12; RA Li M., Conklin B.C., Taracila M.A., Hutton R.A., Skalweit M.J.; RT "Substitutions at position 105 in SHV family beta-lactamases decrease RT catalytic efficiency and cause inhibitor resistance."; RL Antimicrob. Agents Chemother. 56:5678-5686(2012). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS), FUNCTION, AND CATALYTIC ACTIVITY. RC STRAIN=15571; RX PubMed=10231522; DOI=10.1021/bi990136d; RA Kuzin A.P., Nukaga M., Nukaga Y., Hujer A.M., Bonomo R.A., Knox J.R.; RT "Structure of the SHV-1 beta-lactamase."; RL Biochemistry 38:5720-5727(1999). RN [8] {ECO:0007744|PDB:1VM1} RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP TAZOBACTAM, AND ACTIVITY REGULATION. RX PubMed=11327849; DOI=10.1021/bi0022745; RA Kuzin A.P., Nukaga M., Nukaga Y., Hujer A., Bonomo R.A., Knox J.R.; RT "Inhibition of the SHV-1 beta-lactamase by sulfones: crystallographic RT observation of two reaction intermediates with tazobactam."; RL Biochemistry 40:1861-1866(2001). RN [9] {ECO:0007744|PDB:1ONG} RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP PENEM. RX PubMed=14609325; DOI=10.1021/bi034986b; RA Nukaga M., Abe T., Venkatesan A.M., Mansour T.S., Bonomo R.A., Knox J.R.; RT "Inhibition of class A and class C beta-lactamases by penems: RT crystallographic structures of a novel 1,4-thiazepine intermediate."; RL Biochemistry 42:13152-13159(2003). RN [10] {ECO:0007744|PDB:1TDG, ECO:0007744|PDB:1TDL} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 22-286 OF MUTANT GLY-126 IN APO RP FORM AND IN COMPLEX WITH INHIBITOR TAZOBACTAM. RX PubMed=15518561; DOI=10.1021/bi0487903; RA Sun T., Bethel C.R., Bonomo R.A., Knox J.R.; RT "Inhibitor-resistant class A beta-lactamases: consequences of the Ser130- RT to-Gly mutation seen in Apo and tazobactam structures of the SHV-1 RT variant."; RL Biochemistry 43:14111-14117(2004). RN [11] {ECO:0007744|PDB:1RCJ} RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 22-286 OF MUTANT ALA-162 IN RP COMPLEX WITH INHIBITOR TAZOBACTAM. RX PubMed=14744126; DOI=10.1021/bi035985m; RA Padayatti P.S., Helfand M.S., Totir M.A., Carey M.P., Hujer A.M., RA Carey P.R., Bonomo R.A., van den Akker F.; RT "Tazobactam forms a stoichiometric trans-enamine intermediate in the E166A RT variant of SHV-1 beta-lactamase: 1.63 A crystal structure."; RL Biochemistry 43:843-848(2004). RN [12] {ECO:0007744|PDB:1Q2P} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP 6-METHYLIDENE PENEM. RX PubMed=15588091; DOI=10.1021/jm049680x; RA Venkatesan A.M., Gu Y., Dos Santos O., Abe T., Agarwal A., Yang Y., RA Petersen P.J., Weiss W.J., Mansour T.S., Nukaga M., Hujer A.M., RA Bonomo R.A., Knox J.R.; RT "Structure-activity relationship of 6-methylidene penems bearing tricyclic RT heterocycles as broad-spectrum beta-lactamase inhibitors: crystallographic RT structures show unexpected binding of 1,4-thiazepine intermediates."; RL J. Med. Chem. 47:6556-6568(2004). RN [13] {ECO:0007744|PDB:2A3U, ECO:0007744|PDB:2A49} RP X-RAY CRYSTALLOGRAPHY (1.34 ANGSTROMS) OF 22-286 OF MUTANT ALA-162 IN RP COMPLEXES WITH INHIBITORS SULBACTAM AND CLAVULANIC ACID. RX PubMed=16055923; DOI=10.1074/jbc.m505333200; RA Padayatti P.S., Helfand M.S., Totir M.A., Carey M.P., Carey P.R., RA Bonomo R.A., van den Akker F.; RT "High resolution crystal structures of the trans-enamine intermediates RT formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase."; RL J. Biol. Chem. 280:34900-34907(2005). RN [14] {ECO:0007744|PDB:2H0T, ECO:0007744|PDB:2H0Y, ECO:0007744|PDB:2H10} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 22-286 OF MUTANT ALA-162 AND RP DOUBLE MUTANT VAL-65/ALA-162 IN COMPLEXES WITH INHIBITORS. RX PubMed=17002290; DOI=10.1021/bi060990m; RA Totir M.A., Padayatti P.S., Helfand M.S., Carey M.P., Bonomo R.A., RA Carey P.R., van den Akker F.; RT "Effect of the inhibitor-resistant M69V substitution on the structures and RT populations of trans-enamine beta-lactamase intermediates."; RL Biochemistry 45:11895-11904(2006). RN [15] {ECO:0007744|PDB:2H5S} RP X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP PENAM SULFONE SA2-13. RX PubMed=17017804; DOI=10.1021/ja063715w; RA Padayatti P.S., Sheri A., Totir M.A., Helfand M.S., Carey M.P., RA Anderson V.E., Carey P.R., Bethel C.R., Bonomo R.A., Buynak J.D., RA van den Akker F.; RT "Rational design of a beta-lactamase inhibitor achieved via stabilization RT of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 RT complex with a penam sulfone."; RL J. Am. Chem. Soc. 128:13235-13242(2006). RN [16] {ECO:0007744|PDB:2G2U, ECO:0007744|PDB:2G2W} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 22-286 APO FORM AND MUTANT LYS-97 RP IN COMPLEXES WITH S.CLAVULIGERIS BLIP, AND MUTAGENESIS OF ASP-97. RX PubMed=16809340; DOI=10.1074/jbc.m603878200; RA Reynolds K.A., Thomson J.M., Corbett K.D., Bethel C.R., Berger J.M., RA Kirsch J.F., Bonomo R.A., Handel T.M.; RT "Structural and computational characterization of the SHV-1 beta-lactamase- RT beta-lactamase inhibitor protein interface."; RL J. Biol. Chem. 281:26745-26753(2006). RN [17] {ECO:0007744|PDB:3C4O, ECO:0007744|PDB:3C4P} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 22-286, AND INTERACTION WITH RP MUTANT PROTEINS S.CLAVULIGERIS BLIP. RX PubMed=18775544; DOI=10.1016/j.jmb.2008.05.051; RA Reynolds K.A., Hanes M.S., Thomson J.M., Antczak A.J., Berger J.M., RA Bonomo R.A., Kirsch J.F., Handel T.M.; RT "Computational redesign of the SHV-1 beta-lactamase/beta-lactamase RT inhibitor protein interface."; RL J. Mol. Biol. 382:1265-1275(2008). RN [18] {ECO:0007744|PDB:2ZD8} RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP MEROPENEM. RX PubMed=18761444; DOI=10.1021/ja7111146; RA Nukaga M., Bethel C.R., Thomson J.M., Hujer A.M., Distler A., RA Anderson V.E., Knox J.R., Bonomo R.A.; RT "Inhibition of class A beta-lactamases by carbapenems: crystallographic RT observation of two conformations of meropenem in SHV-1."; RL J. Am. Chem. Soc. 130:12656-12662(2008). RN [19] {ECO:0007744|PDB:3D4F} RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH INHIBITOR SULFONE RP LN-1-255, FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF SER-126. RX PubMed=18955486; DOI=10.1074/jbc.m806833200; RA Pattanaik P., Bethel C.R., Hujer A.M., Hujer K.M., Distler A.M., RA Taracila M., Anderson V.E., Fritsche T.R., Jones R.N., Pagadala S.R., RA van den Akker F., Buynak J.D., Bonomo R.A.; RT "Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6- RT alkylidene-2'-substituted penicillin sulfone."; RL J. Biol. Chem. 284:945-953(2009). RN [20] {ECO:0007744|PDB:3MKE, ECO:0007744|PDB:3MKF, ECO:0007744|PDB:3MXR, ECO:0007744|PDB:3MXS} RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 22-286 IN COMPLEXES WITH RP INHIBITOR BORONIC ACID TRANSITION STATE ANALOGS. RX PubMed=21041505; DOI=10.1128/aac.00930-10; RA Ke W., Sampson J.M., Ori C., Prati F., Drawz S.M., Bethel C.R., RA Bonomo R.A., van den Akker F.; RT "Novel insights into the mode of inhibition of class A SHV-1 beta- RT lactamases revealed by boronic acid transition state inhibitors."; RL Antimicrob. Agents Chemother. 55:174-183(2011). RN [21] {ECO:0007744|PDB:3OPH, ECO:0007744|PDB:3OPL, ECO:0007744|PDB:3OPP, ECO:0007744|PDB:3OPR} RP X-RAY CRYSTALLOGRAPHY (1.34 ANGSTROMS) OF MUTANTS SER-160 AND HIS-160 IN RP COMPLEXES WITH INHIBITOR SA2-13, AND MUTAGENESIS OF ARG-160. RX PubMed=21357298; DOI=10.1128/aac.01360-10; RA Sampson J.M., Ke W., Bethel C.R., Pagadala S.R., Nottingham M.D., RA Bonomo R.A., Buynak J.D., van den Akker F.; RT "Ligand-dependent disorder of the Omega loop observed in extended-spectrum RT SHV-type beta-lactamase."; RL Antimicrob. Agents Chemother. 55:2303-2309(2011). RN [22] {ECO:0007744|PDB:3N4I} RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 22-286 OF MUTANT GLU-97 IN RP COMPLEX WITH S.CLAVULIGERIS BLIP, AND MUTAGENESIS OF ASP-97. RX PubMed=21294157; DOI=10.1002/prot.22961; RA Hanes M.S., Reynolds K.A., McNamara C., Ghosh P., Bonomo R.A., Kirsch J.F., RA Handel T.M.; RT "Specificity and cooperativity at beta-lactamase position 104 in TEM-1/BLIP RT and SHV-1/BLIP interactions."; RL Proteins 79:1267-1276(2011). RN [23] {ECO:0007744|PDB:3V50, ECO:0007744|PDB:3V5M} RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 22-286 OF MUTANT GLY-126 IN RP COMPLEX WITH INHIBITOR SA2-13. RX PubMed=22438274; DOI=10.1002/cmdc.201200006; RA Ke W., Rodkey E.A., Sampson J.M., Skalweit M.J., Sheri A., Pagadala S.R., RA Nottingham M.D., Buynak J.D., Bonomo R.A., van den Akker F.; RT "The importance of the trans-enamine intermediate as a beta-lactamase RT inhibition strategy probed in inhibitor-resistant SHV beta-lactamase RT variants."; RL ChemMedChem 7:1002-1008(2012). RN [24] {ECO:0007744|PDB:4FD8, ECO:0007744|PDB:4FH2, ECO:0007744|PDB:4FH4} RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 22-286 OF MUTANT CYS-66 IN RP COMPLEX WITH INHIBITOR SULBACTAM, ACTIVITY REGULATION, AND MUTAGENESIS OF RP SER-66. RX PubMed=22974281; DOI=10.1021/ja3073676; RA Rodkey E.A., Drawz S.M., Sampson J.M., Bethel C.R., Bonomo R.A., RA van den Akker F.; RT "Crystal structure of a preacylation complex of the beta-lactamase RT inhibitor sulbactam bound to a sulfenamide bond-containing thiol-beta- RT lactamase."; RL J. Am. Chem. Soc. 134:16798-16804(2012). RN [25] {ECO:0007744|PDB:4GD6, ECO:0007744|PDB:4GD8, ECO:0007744|PDB:4GDB} RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) IN COMPLEXES WITH INHIBITORS PENEM RP AND PENAM SULFONE SA1-204 AND LN1-255, FUNCTION, ACTIVITY REGULATION, AND RP MUTAGENESIS OF SER-126; ARG-160 AND ASP-175. RX PubMed=23145056; DOI=10.1371/journal.pone.0049035; RA Ke W., Pattanaik P., Bethel C.R., Sheri A., Buynak J.D., Bonomo R.A., RA van den Akker F.; RT "Structures of SHV-1 beta-lactamase with penem and penam sulfone inhibitors RT that form cyclic intermediates stabilized by carbonyl conjugation."; RL PLoS ONE 7:e49035-e49035(2012). RN [26] {ECO:0007744|PDB:4FCF} RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 22-286 OF MUTANT ARG-230, RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MUTAGENESIS OF LYS-230. RX PubMed=23252553; DOI=10.1021/jm301490d; RA Winkler M.L., Rodkey E.A., Taracila M.A., Drawz S.M., Bethel C.R., RA Papp-Wallace K.M., Smith K.M., Xu Y., Dwulit-Smith J.R., Romagnoli C., RA Caselli E., Prati F., van den Akker F., Bonomo R.A.; RT "Design and exploration of novel boronic acid inhibitors reveals important RT interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) RT beta-lactamase."; RL J. Med. Chem. 56:1084-1097(2013). RN [27] {ECO:0007744|PDB:4JPM} RP X-RAY CRYSTALLOGRAPHY (1.14 ANGSTROMS) IN COMPLEX WITH SULFONE INHIBITOR, RP AND ACTIVITY REGULATION. RX PubMed=24219313; DOI=10.1021/ja403598g; RA Rodkey E.A., McLeod D.C., Bethel C.R., Smith K.M., Xu Y., Chai W., Che T., RA Carey P.R., Bonomo R.A., van den Akker F., Buynak J.D.; RT "beta-Lactamase inhibition by 7-alkylidenecephalosporin sulfones: allylic RT transposition and formation of an unprecedented stabilized acyl-enzyme."; RL J. Am. Chem. Soc. 135:18358-18369(2013). RN [28] {ECO:0007744|PDB:4MBF, ECO:0007744|PDB:4MBH, ECO:0007744|PDB:4MBK} RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 22-286 OF APO FORM AND MUTANT RP ARG-230 IN COMPLEXES WITH INHIBITOR PENAM SULFONES. RX PubMed=24454944; DOI=10.1371/journal.pone.0085892; RA Rodkey E.A., Winkler M.L., Bethel C.R., Pagadala S.R., Buynak J.D., RA Bonomo R.A., van den Akker F.; RT "Penam sulfones and beta-lactamase inhibition: SA2-13 and the importance of RT the C2 side chain length and composition."; RL PLoS ONE 9:e85892-e85892(2014). RN [29] {ECO:0007744|PDB:4R3B} RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP SULFONE. RX PubMed=25536850; DOI=10.1021/bi501197t; RA Che T., Rodkey E.A., Bethel C.R., Shanmugam S., Ding Z., Pusztai-Carey M., RA Nottingham M., Chai W., Buynak J.D., Bonomo R.A., van den Akker F., RA Carey P.R.; RT "Detecting a quasi-stable imine species on the reaction pathway of SHV-1 RT beta-lactamase and 6beta-(hydroxymethyl)penicillanic acid sulfone."; RL Biochemistry 54:734-743(2015). RN [30] {ECO:0007744|PDB:4ZAM} RP X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP AVIBACTAM. RX PubMed=26340563; DOI=10.1371/journal.pone.0136813; RA Krishnan N.P., Nguyen N.Q., Papp-Wallace K.M., Bonomo R.A., RA van den Akker F.; RT "Inhibition of Klebsiella beta-Lactamases (SHV-1 and KPC-2) by Avibactam: A RT Structural Study."; RL PLoS ONE 10:e0136813-e0136813(2015). RN [31] {ECO:0007744|PDB:5EE8} RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 22-286 IN COMPLEX WITH INHIBITOR RP BORONIC ACID TRANSITION STATE ANALOG. RX PubMed=26729491; DOI=10.1128/aac.02643-15; RA Nguyen N.Q., Krishnan N.P., Rojas L.J., Prati F., Caselli E., Romagnoli C., RA Bonomo R.A., van den Akker F.; RT "Crystal Structures of KPC-2 and SHV-1 beta-Lactamases in Complex with the RT Boronic Acid Transition State Analog S02030."; RL Antimicrob. Agents Chemother. 60:1760-1766(2016). CC -!- FUNCTION: Broad-spectrum beta-lactamase which confers resistance to CC penicillins, as well as first- and third-generation cephalosporins CC (PubMed:10639363, PubMed:18955486, PubMed:19351161, PubMed:22908166, CC PubMed:23145056, PubMed:23252553). Has nitrocefin-hydrolyzing activity CC (PubMed:10231522, PubMed:19351161, PubMed:23252553). Inactive against CC the cephalosporins, cefotaxime and cefoxitin, and the carbapenem, CC meropenem (PubMed:10639363, PubMed:19351161). CC {ECO:0000269|PubMed:10231522, ECO:0000269|PubMed:10639363, CC ECO:0000269|PubMed:18955486, ECO:0000269|PubMed:19351161, CC ECO:0000269|PubMed:22908166, ECO:0000269|PubMed:23145056, CC ECO:0000269|PubMed:23252553}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-lactam + H2O = a substituted beta-amino acid; CC Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627, CC ChEBI:CHEBI:140347; EC=3.5.2.6; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10101, ECO:0000269|PubMed:10231522, CC ECO:0000269|PubMed:19351161, ECO:0000269|PubMed:22908166, CC ECO:0000269|PubMed:23252553}; CC -!- ACTIVITY REGULATION: Inhibited by the beta-lactamase-blocking agents CC clavulanic acid, sulbactam, avibactam or tazobactam, or SA1-204 or LN1- CC 255 via a covalent binding to Ser-66 (PubMed:11327849, PubMed:18955486, CC PubMed:19351161, PubMed:22908166, PubMed:22974281, PubMed:23145056, CC PubMed:23252553, PubMed:24219313, PubMed:26340563). Inhibitors SA1-204 CC and LN1-255 may be approximately 16-fold more effective than tazobactam CC (PubMed:23145056). May also be inhibited by tazobactam via a covalent CC binding to Ser-126 (PubMed:11327849). {ECO:0000269|PubMed:11327849, CC ECO:0000269|PubMed:18955486, ECO:0000269|PubMed:19351161, CC ECO:0000269|PubMed:22908166, ECO:0000269|PubMed:22974281, CC ECO:0000269|PubMed:23145056, ECO:0000269|PubMed:23252553, CC ECO:0000269|PubMed:24219313, ECO:0000269|PubMed:26340563}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=183 uM for ampicillin (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:19351161}; CC KM=77 uM for piperacillin (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:19351161}; CC KM=75 uM for piperacillin (at pH 7.4) {ECO:0000269|PubMed:23252553}; CC KM=21 uM for nitrocefin (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:19351161}; CC KM=25 uM for nitrocefin (at pH 7.4) {ECO:0000269|PubMed:23252553}; CC KM=29 uM for cephalothin (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:19351161}; CC KM=49 uM for cephalothin (at pH 7.4) {ECO:0000269|PubMed:23252553}; CC Note=kcat is 3100 sec(-1) with ampicillin as substrate (at pH 7.4 and CC 25 degrees Celsius) (PubMed:19351161). kcat is 898 sec(-1) with CC piperacillin as substrate (at pH 7.4 and 25 degrees Celsius) CC (PubMed:19351161). kcat is 1179 sec(-1) with piperacillin as CC substrate (at pH 7.4) (PubMed:23252553). kcat is 237 sec(-1) with CC nitrocefin as substrate (at pH 7.4 and 25 degrees Celsius) CC (PubMed:19351161). kcat is 348 sec(-1) with nitrocefin as substrate CC (at pH 7.4) (PubMed:23252553). kcat is 14 sec(-1) with cephalothin as CC substrate (at pH 7.4 and 25 degrees Celsius) (PubMed:19351161). kcat CC is 43 sec(-1) with nitrocefin as substrate (at pH 7.4) CC (PubMed:23252553). {ECO:0000269|PubMed:19351161, CC ECO:0000269|PubMed:23252553}; CC -!- SUBUNIT: Interacts with S.clavuligerus beta-lactamase inhibitor protein CC BLIP. {ECO:0000269|PubMed:16809340, ECO:0000269|PubMed:18775544, CC ECO:0000269|PubMed:21294157}. CC -!- INDUCTION: Increased expression in clinical isolate strain 15571, in CC concert with reduced expression of a 45-kDa outer membrane protein, CC confers increased resistance to ceftazidime. CC {ECO:0000269|PubMed:10639363}. CC -!- MISCELLANEOUS: The class A beta-lactamase family has a specific amino- CC acid numbering system, sometimes called Ambler or ABL numbering and CC often misspelt as Amber (PubMed:2039479). A multiple sequence alignment CC was used to derive a consensus sequence and then the consensus was CC numbered taking into account insertions and deletions (PubMed:2039479). CC This allows use of identical numbers, e.g. for active site residues, CC despite differences in protein length (PubMed:2039479). UniProt always CC uses natural numbering of residues, hence there appear to be CC differences in numbering between this entry and some papers CC (PubMed:2039479). {ECO:0000269|PubMed:2039479}. CC -!- SIMILARITY: Belongs to the class-A beta-lactamase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M59181; AAA26087.1; -; Genomic_DNA. DR EMBL; X98098; CAA66726.1; -; Genomic_DNA. DR EMBL; X98099; CAA66727.1; -; Genomic_DNA. DR EMBL; X98100; CAA66728.1; -; Genomic_DNA. DR EMBL; AF124984; AAD18054.1; -; Genomic_DNA. DR PIR; A44996; A44996. DR RefSeq; WP_001620095.1; NZ_AP021909.1. DR PDB; 1ONG; X-ray; 1.10 A; A=22-286. DR PDB; 1Q2P; X-ray; 2.00 A; A=22-286. DR PDB; 1RCJ; X-ray; 1.63 A; A=22-286. DR PDB; 1SHV; X-ray; 1.98 A; A=22-286. DR PDB; 1TDG; X-ray; 1.80 A; A=22-286. DR PDB; 1TDL; X-ray; 1.80 A; A=22-286. DR PDB; 1VM1; X-ray; 2.02 A; A=22-286. DR PDB; 2A3U; X-ray; 1.34 A; A=22-286. DR PDB; 2A49; X-ray; 1.43 A; A=22-286. DR PDB; 2G2U; X-ray; 1.60 A; A=22-286. DR PDB; 2G2W; X-ray; 1.80 A; A=22-286. DR PDB; 2H0T; X-ray; 1.60 A; A=22-286. DR PDB; 2H0Y; X-ray; 1.70 A; A=22-286. DR PDB; 2H10; X-ray; 1.75 A; A=22-286. DR PDB; 2H5S; X-ray; 1.28 A; A=22-286. DR PDB; 2ZD8; X-ray; 1.05 A; A=22-286. DR PDB; 3C4O; X-ray; 1.70 A; A=22-286. DR PDB; 3C4P; X-ray; 1.75 A; A=22-286. DR PDB; 3D4F; X-ray; 1.55 A; A=1-286. DR PDB; 3MKE; X-ray; 1.75 A; A=22-286. DR PDB; 3MKF; X-ray; 1.33 A; A=22-286. DR PDB; 3MXR; X-ray; 1.30 A; A=22-286. DR PDB; 3MXS; X-ray; 1.24 A; A=22-286. DR PDB; 3N4I; X-ray; 1.56 A; A=22-286. DR PDB; 3OPH; X-ray; 1.34 A; A=1-286. DR PDB; 3OPL; X-ray; 1.80 A; A=1-286. DR PDB; 3OPP; X-ray; 1.80 A; A=1-286. DR PDB; 3OPR; X-ray; 1.65 A; A=1-286. DR PDB; 3V50; X-ray; 1.45 A; A=22-286. DR PDB; 3V5M; X-ray; 1.30 A; A=22-286. DR PDB; 4FCF; X-ray; 1.09 A; A=22-286. DR PDB; 4FD8; X-ray; 1.52 A; A=22-286. DR PDB; 4FH2; X-ray; 1.44 A; A=22-286. DR PDB; 4FH4; X-ray; 1.09 A; A=22-286. DR PDB; 4GD6; X-ray; 1.53 A; A=1-286. DR PDB; 4GD8; X-ray; 1.60 A; A=1-286. DR PDB; 4GDB; X-ray; 1.84 A; A=1-286. DR PDB; 4JPM; X-ray; 1.14 A; A=1-286. DR PDB; 4MBF; X-ray; 1.54 A; A=22-286. DR PDB; 4MBH; X-ray; 1.22 A; A=22-286. DR PDB; 4MBK; X-ray; 1.46 A; A=22-286. DR PDB; 4R3B; X-ray; 1.37 A; A=22-286. DR PDB; 4ZAM; X-ray; 1.42 A; A=22-286. DR PDB; 5EE8; X-ray; 1.54 A; A=22-286. DR AlphaFoldDB; P0AD64; -. DR MDRepo; P0AD64; -. DR SMR; P0AD64; -. DR BindingDB; P0AD64; -. DR ChEMBL; CHEMBL5094; -. DR DrugBank; DB08116; (3R)-4-{[(3,4-dihydroxyphenyl)acetyl]oxy}-N-(2-formylindolizin-3-yl)-3-sulfino-D-valine. DR DrugBank; DB03970; (7R)-7-(6,7-Dihydro-5H-cyclopenta[d]imidazo[2,1-b][1,3]thiazol-2-yl)-2,7-dihydro-1,4-thiazepine-3,6-dicarboxylic acid. DR DrugBank; DB09060; Avibactam. DR DrugBank; DB12107; Vaborbactam. DR DrugCentral; P0AD64; -. DR CARD; ARO:3001059; SHV-1; ARO:0001004; antibiotic inactivation. DR BRENDA; 3.5.2.6; 2814. DR SABIO-RK; P0AD64; -. DR EvolutionaryTrace; P0AD64; -. DR GO; GO:0008800; F:beta-lactamase activity; EXP:UniProtKB. DR GO; GO:0030655; P:beta-lactam antibiotic catabolic process; IEA:InterPro. DR GO; GO:0046677; P:response to antibiotic; IEA:InterPro. DR Gene3D; 3.40.710.10; DD-peptidase/beta-lactamase superfamily; 1. DR InterPro; IPR012338; Beta-lactam/transpept-like. DR InterPro; IPR045155; Beta-lactam_cat. DR InterPro; IPR000871; Beta-lactam_class-A. DR InterPro; IPR023650; Beta-lactam_class-A_AS. DR NCBIfam; NF033103; bla_class_A; 1. DR NCBIfam; NF000285; SHV; 1. DR NCBIfam; NF012143; SHV_LEN_OKP; 1. DR PANTHER; PTHR35333; BETA-LACTAMASE; 1. DR PANTHER; PTHR35333:SF3; BETA-LACTAMASE-TYPE TRANSPEPTIDASE FOLD CONTAINING PROTEIN; 1. DR Pfam; PF13354; Beta-lactamase2; 1. DR PRINTS; PR00118; BLACTAMASEA. DR SUPFAM; SSF56601; beta-lactamase/transpeptidase-like; 1. DR PROSITE; PS00146; BETA_LACTAMASE_A; 1. DR PDBsum; 1ONG; -. DR PDBsum; 1Q2P; -. DR PDBsum; 1RCJ; -. DR PDBsum; 1SHV; -. DR PDBsum; 1TDG; -. DR PDBsum; 1TDL; -. DR PDBsum; 1VM1; -. DR PDBsum; 2A3U; -. DR PDBsum; 2A49; -. DR PDBsum; 2G2U; -. DR PDBsum; 2G2W; -. DR PDBsum; 2H0T; -. DR PDBsum; 2H0Y; -. DR PDBsum; 2H10; -. DR PDBsum; 2H5S; -. DR PDBsum; 2ZD8; -. DR PDBsum; 3C4O; -. DR PDBsum; 3C4P; -. DR PDBsum; 3D4F; -. DR PDBsum; 3MKE; -. DR PDBsum; 3MKF; -. DR PDBsum; 3MXR; -. DR PDBsum; 3MXS; -. DR PDBsum; 3N4I; -. DR PDBsum; 3OPH; -. DR PDBsum; 3OPL; -. DR PDBsum; 3OPP; -. DR PDBsum; 3OPR; -. DR PDBsum; 3V50; -. DR PDBsum; 3V5M; -. DR PDBsum; 4FCF; -. DR PDBsum; 4FD8; -. DR PDBsum; 4FH2; -. DR PDBsum; 4FH4; -. DR PDBsum; 4GD6; -. DR PDBsum; 4GD8; -. DR PDBsum; 4GDB; -. DR PDBsum; 4JPM; -. DR PDBsum; 4MBF; -. DR PDBsum; 4MBH; -. DR PDBsum; 4MBK; -. DR PDBsum; 4R3B; -. DR PDBsum; 4ZAM; -. DR PDBsum; 5EE8; -. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic resistance; Disulfide bond; Hydrolase; Plasmid; KW Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..286 FT /note="Beta-lactamase SHV-1" FT /id="PRO_0000043362" FT ACT_SITE 66 FT /note="Nucleophile; acyl-ester intermediate" FT /evidence="ECO:0000250|UniProtKB:P62593" FT ACT_SITE 69 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P62593" FT ACT_SITE 126 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P62593" FT ACT_SITE 162 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P62593" FT BINDING 69 FT /ligand="a beta-lactam" FT /ligand_id="ChEBI:CHEBI:35627" FT /evidence="ECO:0000250|UniProtKB:A0A5R8T042" FT BINDING 126 FT /ligand="a beta-lactam" FT /ligand_id="ChEBI:CHEBI:35627" FT /evidence="ECO:0000250|UniProtKB:A0A5R8T042" FT BINDING 162 FT /ligand="a beta-lactam" FT /ligand_id="ChEBI:CHEBI:35627" FT /evidence="ECO:0000250|UniProtKB:A0A5R8T042" FT DISULFID 73..119 FT /evidence="ECO:0007744|PDB:2ZD8" FT MUTAGEN 66 FT /note="S->C: Forms sulfenamide bond with Lys-69." FT /evidence="ECO:0000269|PubMed:22974281" FT MUTAGEN 97 FT /note="D->E: About 1000-fold increase in binding affinity FT of S.clavuligerus beta-lactamase inhibitory protein BLIP." FT /evidence="ECO:0000269|PubMed:16809340, FT ECO:0000269|PubMed:21294157" FT MUTAGEN 97 FT /note="D->K: About 2-fold increase in binding affinity of FT S.clavuligerus beta-lactamase inhibitory protein BLIP." FT /evidence="ECO:0000269|PubMed:16809340" FT MUTAGEN 101 FT /note="Y->A,C: Reduces resistance to ampicillin about FT 100-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->D,E,I,R,T: Reduces resistance to ampicillin about FT 16-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->E: Reduces catalytic efficiency toward FT ampicillin." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->F: Resistance to ampicillin unchanged in FT DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->G,K,N,V: Reduces resistance to ampicillin about FT 30-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->H,Q: Reduces resistance to ampicillin about FT 60-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->L: Reduces resistance to ampicillin about FT 500-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->M,S: Reduces resistance to ampicillin about FT 8-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->P: Reduces resistance to ampicillin about 4-fold FT in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 101 FT /note="Y->W: Reduces resistance to ampicillin about 2-fold FT in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:22908166" FT MUTAGEN 126 FT /note="S->G: Reduces resistance to piperacillin about FT 8-fold in DH10BE.coli strain. Decreases resistance to FT combined piperacillin and tazobactam between 4- and 16-fold FT in DH10BE.coli strain. Increases resistance to combined FT piperacillin and inhibitor LN-1-255 about 2-fold in FT DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:18955486, FT ECO:0000269|PubMed:23145056" FT MUTAGEN 160 FT /note="R->H: Reduces resistance to piperacillin about FT 2-fold in DH10BE.coli strain. Decreases resistance to FT combined piperacillin and tazobactam about 500-fold in FT DH10BE.coli strain. About 7-fold increase in binding FT affinity of inhibitor SA2-13; about 2-fold increase in FT binding affinity of inhibitor tazobactam." FT /evidence="ECO:0000269|PubMed:21357298, FT ECO:0000269|PubMed:23145056" FT MUTAGEN 160 FT /note="R->S: Reduces resistance to piperacillin about FT 60-fold in DH10BE.coli strain. Decreases resistance to FT combined piperacillin and tazobactam about 1000-fold in FT DH10BE.coli strain. About 3-fold increase in binding FT affinity of inhibitor SA2-13; about 2-fold increase in FT binding affinity of inhibitor tazobactam." FT /evidence="ECO:0000269|PubMed:21357298" FT MUTAGEN 175 FT /note="D->N: Reduces resistance to piperacillin about FT 16-fold in DH10BE.coli strain. Decreases resistance to FT combined piperacillin and tazobactam about 1000-fold in FT DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:23145056" FT MUTAGEN 230 FT /note="K->A: Reduces resistance to penicillins about FT 500-fold in DH10BE.coli strain; reduces resistance to FT cephalothin about 30-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:23252553" FT MUTAGEN 230 FT /note="K->C,D,E,F,G,H,I,L,M,N,P,Q,S,T,V,W,Y: Almost FT abolishes resistance to penicillins or cephalothin in FT DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:23252553" FT MUTAGEN 230 FT /note="K->R: Resistance to penicillins almost unaffected in FT DH10BE.coli strain; reduces resistance to cephalothin about FT 16-fold in DH10BE.coli strain. Increases resistance to FT combined ampicillin and clavulanic acid 4-fold in FT DH10BE.coli strain. Reduces binding affinity for clavulanic FT acid, tazobactam and sulbactam about 6-fold, 2-fold, and FT 3-fold, respectively." FT /evidence="ECO:0000269|PubMed:23252553" FT MUTAGEN 270 FT /note="N->A,L,I: Reduces resistance to penicillins about FT 60-fold and to cephalothin about 120-fold in DH10BE.coli FT strain. Decreases resistance to combined ampicillin and FT clavulanic acid about 8-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:19351161" FT MUTAGEN 270 FT /note="N->D: Reduces resistance to penicillins about 2-fold FT and to cephalothin about 8-fold, in DH10BE.coli strain. FT Increases resistance to combined ampicillin and clavulanic FT acid 4-fold in DH10B strain. Slightly reduces catalytic FT efficiency with respect to penicillins, cephalothin and FT nitrocefin. Reduces inhibition by clavulanic acid about FT 5-fold. Reduces binding affinity for meropenem about FT 40-fold." FT /evidence="ECO:0000269|PubMed:19351161" FT MUTAGEN 270 FT /note="N->G,S: Reduces resistance to penicillins about FT 4-fold and to cephalothin about 8-fold in DH10BE.coli FT strain. No effect on resistance to combined ampicillin and FT clavulanic acid in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:19351161" FT MUTAGEN 270 FT /note="N->K,R,Y,F: Reduces resistance to penicillins about FT 250-fold and to cephalothin about 250-fold in DH10BE.coli FT strain. Decreases resistance to combined ampicillin and FT clavulanic acid about 16-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:19351161" FT MUTAGEN 270 FT /note="N->M,P,W: Reduces resistance to penicillins about FT 1000-fold and cephalothin about 500-fold in DH10BE.coli FT strain. Abolishes resistance to combined ampicillin and FT clavulanic acid in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:19351161" FT MUTAGEN 270 FT /note="N->V,Q,E,C,T,H: Reduces resistance to penicillins FT about 8-fold and to cephalothin about 8-fold in DH10BE.coli FT strain. Decreases resistance to combined ampicillin and FT clavulanic acid about 2-fold in DH10BE.coli strain." FT /evidence="ECO:0000269|PubMed:19351161" FT CONFLICT 112 FT /note="G -> A (in Ref. 1; AAA26087)" FT /evidence="ECO:0000305" FT CONFLICT 188..189 FT /note="KL -> NVG (in Ref. 1; AAA26087)" FT /evidence="ECO:0000305" FT CONFLICT 278 FT /note="A -> K (in Ref. 1; AAA26087)" FT /evidence="ECO:0000305" FT CONFLICT 281 FT /note="I -> Y (in Ref. 1; AAA26087)" FT /evidence="ECO:0000305" FT HELIX 25..36 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 38..46 FT /evidence="ECO:0007829|PDB:2ZD8" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 52..57 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 68..81 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 95..97 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 105..108 FT /evidence="ECO:0007829|PDB:2ZD8" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 115..125 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 128..137 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 140..150 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 179..191 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 192..195 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 197..208 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 214..220 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 226..233 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 239..247 FT /evidence="ECO:0007829|PDB:2ZD8" FT STRAND 253..261 FT /evidence="ECO:0007829|PDB:2ZD8" FT HELIX 266..282 FT /evidence="ECO:0007829|PDB:2ZD8" FT TURN 283..285 FT /evidence="ECO:0007829|PDB:3N4I" SQ SEQUENCE 286 AA; 31224 MW; C78F42667E698E6C CRC64; MRYIRLCIIS LLATLPLAVH ASPQPLEQIK LSESQLSGRV GMIEMDLASG RTLTAWRADE RFPMMSTFKV VLCGAVLARV DAGDEQLERK IHYRQQDLVD YSPVSEKHLA DGMTVGELCA AAITMSDNSA ANLLLATVGG PAGLTAFLRQ IGDNVTRLDR WETELNEALP GDARDTTTPA SMAATLRKLL TSQRLSARSQ RQLLQWMVDD RVAGPLIRSV LPAGWFIADK TGAGERGARG IVALLGPNNK AERIVVIYLR DTPASMAERN QQIAGIGAAL IEHWQR //