ID   BLAS1_SERMA             Reviewed;         294 AA.
AC   P52682; Q54488;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2025, sequence version 2.
DT   04-NOV-2026, entry version 92.
DE   RecName: Full=Beta-lactamase SME-1 {ECO:0000303|PubMed:21840669, ECO:0000303|PubMed:7793864, ECO:0000303|PubMed:8092824};
DE            EC=3.5.2.6 {ECO:0000269|PubMed:11036019, ECO:0000269|PubMed:8092824};
DE   Flags: Precursor;
GN   Name=SME-1 {ECO:0000303|PubMed:21840669, ECO:0000303|PubMed:7793864,
GN   ECO:0000303|PubMed:8092824};
GN   Synonyms=blaSME-1 {ECO:0000312|EMBL:AGZ03855.1}, blaSME-4
GN   {ECO:0000312|EMBL:AHA49908.1}, blaSME1 {ECO:0000312|EMBL:AEJ79644.1},
GN   bpl-1, bplA, sme-2 {ECO:0000312|EMBL:AAB03414.1}, smeA;
OS   Serratia marcescens.
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Enterobacterales; Yersiniaceae; Serratia.
OX   NCBI_TaxID=615;
RN   [1] {ECO:0000312|EMBL:AAB03414.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 28-38, FUNCTION,
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   INDUCTION.
RC   STRAIN=S6 {ECO:0000312|EMBL:AAB03414.1};
RX   PubMed=8092824; DOI=10.1128/aac.38.6.1262;
RA   Naas T., Vandel L., Sougakoff W., Livermore D.M., Nordmann P.;
RT   "Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing
RT   class A beta-lactamase, Sme-1, from Serratia marcescens S6.";
RL   Antimicrob. Agents Chemother. 38:1262-1270(1994).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-32, AND INDUCTION BY BETA-LACTAMS.
RC   STRAIN=S6;
RX   PubMed=7793864; DOI=10.1128/aac.39.3.629;
RA   Naas T., Livermore D.M., Nordmann P.;
RT   "Characterization of an LysR family protein, SmeR from Serratia marcescens
RT   S6, its effect on expression of the carbapenem-hydrolyzing beta-lactamase
RT   Sme-1, and comparison of this regulator with other beta-lactamase
RT   regulators.";
RL   Antimicrob. Agents Chemother. 39:629-637(1995).
RN   [3] {ECO:0000312|EMBL:AAB03414.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=S6 {ECO:0000312|EMBL:AAB03414.1};
RA   Rasmussen B.A., Keeney D., Cohen C.;
RT   "Carbapenem-hydrolyzing beta-lactamase, Sme-2.";
RL   Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000312|EMBL:AEJ79644.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=SMDET-2 {ECO:0000312|EMBL:AEJ79644.1};
RX   PubMed=21840669; DOI=10.1016/j.diagmicrobio.2011.06.007;
RA   Fairfax M.R., Queenan A.M., Lephart P.R., Kaye K.S., Dror M., Arnous N.,
RA   Salimnia T.T., Mitchell R.A., Alangaden G., Salimnia H.;
RT   "Detection of 2 SME-1 carbapenemase-producing Serratia marcescens in
RT   Detroit.";
RL   Diagn. Microbiol. Infect. Dis. 71:325-326(2011).
RN   [5] {ECO:0000312|EMBL:AHA49908.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=41727R {ECO:0000312|EMBL:AHA49908.1};
RA   Farrell S.E., Castanheira M., Jones R.N.;
RT   "Characterization of carbapenem resistant isolates from 2012.";
RL   Submitted (JUL-2013) to the EMBL/GenBank/DDBJ databases.
RN   [6] {ECO:0000312|EMBL:AGZ03855.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=N12-0620 {ECO:0000312|EMBL:AGZ03855.1};
RX   PubMed=24659751; DOI=10.1093/jac/dku040;
RA   Mataseje L.F., Boyd D.A., Delport J., Hoang L., Imperial M., Lefebvre B.,
RA   Kuhn M., Van Caeseele P., Willey B.M., Mulvey M.R.;
RT   "Serratia marcescens harbouring SME-type class A carbapenemases in Canada
RT   and the presence of blaSME on a novel genomic island, SmarGI1-1.";
RL   J. Antimicrob. Chemother. 69:1825-1829(2014).
RN   [7] {ECO:0000305}
RP   AMINO ACID NUMBERING SCHEME.
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   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP   PROPERTIES, AND MUTAGENESIS OF VAL-207.
RX   PubMed=11036019; DOI=10.1128/aac.44.11.3035-3039.2000;
RA   Queenan A.M., Torres-Viera C., Gold H.S., Carmeli Y., Eliopoulos G.M.,
RA   Moellering R.C. Jr., Quinn J.P., Hindler J., Medeiros A.A., Bush K.;
RT   "SME-type carbapenem-hydrolyzing class A beta-lactamases from
RT   geographically diverse Serratia marcescens strains.";
RL   Antimicrob. Agents Chemother. 44:3035-3039(2000).
RN   [9] {ECO:0007744|PDB:1DY6}
RP   X-RAY CRYSTALLOGRAPHY, FUNCTION, DISULFIDE BOND, AND MUTAGENESIS OF CYS-72.
RX   PubMed=11807251; DOI=10.1107/s0907444901019606;
RA   Sougakoff W., L'Hermite G., Pernot L., Naas T., Guillet V., Nordmann P.,
RA   Jarlier V., Delettre J.;
RT   "Structure of the imipenem-hydrolyzing class A beta-lactamase SME-1 from
RT   Serratia marcescens.";
RL   Acta Crystallogr. D 58:267-274(2002).
CC   -!- FUNCTION: Class A beta-lactamase which confers resistance to the beta-
CC       lactam antibiotics, including penicillins, some cephalosporins and
CC       carbapenems, to JM109 strain E.coli (PubMed:11807251, PubMed:8092824).
CC       Acts via hydrolysis of the beta-lactam ring (PubMed:11036019,
CC       PubMed:8092824). Has penicillin-, cephalosporin- and carbapenem-
CC       hydrolyzing activities (PubMed:11036019). {ECO:0000269|PubMed:11036019,
CC       ECO:0000269|PubMed:11807251, ECO:0000269|PubMed:8092824}.
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;
CC         Evidence={ECO:0000269|PubMed:11036019, ECO:0000269|PubMed:8092824};
CC   -!- ACTIVITY REGULATION: Partially inhibited by the beta-lactamase-blocking
CC       agents, clavulanic acid and tazobactam (PubMed:11036019,
CC       PubMed:8092824). Not inhibited by EDTA (PubMed:11036019,
CC       PubMed:8092824). {ECO:0000269|PubMed:11036019,
CC       ECO:0000269|PubMed:8092824}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=16.7 uM for penicillin (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=488 uM for ampicillin (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=770 uM for cephaloridine (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=202 uM for imipenem (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=13.4 uM for meropenem (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=259 uM for aztreonam (at pH 7.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:11036019};
CC         KM=62 uM for aztreonam (at pH 7.0) {ECO:0000269|PubMed:8092824};
CC         Note=kcat is 19.3 sec(-1) with penicillin as substrate (at pH 7.0 and
CC         25 degrees Celsius) (PubMed:11036019). kcat is 181 sec(-1) with
CC         ampicillin as substrate (at pH 7.0 and 25 degrees Celsius)
CC         (PubMed:11036019). kcat is 980 sec(-1) with cephaloridine as
CC         substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:11036019). kcat
CC         is 104 sec(-1) with imipenem as substrate (at pH 7.0 and 25 degrees
CC         Celsius) (PubMed:11036019). kcat is 8.9 sec(-1) with meropenem as
CC         substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:11036019). kcat
CC         is 108 sec(-1) with aztreonam as substrate (at pH 7.0 and 25 degrees
CC         Celsius) (PubMed:11036019). {ECO:0000269|PubMed:11036019};
CC   -!- INDUCTION: Up-regulated by the carbapenem, imipenem (PubMed:7793864).
CC       Expression probably regulated by upstream promoter elements
CC       (PubMed:8092824). {ECO:0000269|PubMed:7793864,
CC       ECO:0000269|PubMed:8092824}.
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. A multiple sequence alignment was used to
CC       derive a consensus sequence and then the consensus was numbered taking
CC       into account insertions and deletions. This allows use of identical
CC       numbers, e.g. for active site residues, despite differences in protein
CC       length. UniProt always uses natural numbering of residues, hence there
CC       appear to be differences in numbering between this entry and some
CC       papers. {ECO:0000305|PubMed:2039479}.
CC   -!- SIMILARITY: Belongs to the class-A beta-lactamase family.
CC       {ECO:0000305}.
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DR   EMBL; U60295; AAB03414.1; -; Genomic_DNA.
DR   EMBL; JF974075; AEJ79644.1; -; Genomic_DNA.
DR   EMBL; KF615855; AGZ03855.1; -; Genomic_DNA.
DR   EMBL; KF481967; AHA49908.1; -; Genomic_DNA.
DR   EMBL; Z28968; CAA82281.1; -; Genomic_DNA.
DR   EMBL; Z30237; CAA82944.1; -; Genomic_DNA.
DR   PIR; S44080; S44080.
DR   RefSeq; WP_063864730.1; NG_050137.1.
DR   PDB; 1DY6; X-ray; 2.13 A; A/B=28-294.
DR   PDB; 9IL7; X-ray; 2.40 A; A/B=28-294.
DR   PDB; 9IL8; X-ray; 2.30 A; A/B=28-294.
DR   PDB; 9IL9; X-ray; 2.28 A; A/B=28-294.
DR   PDB; 9ILE; X-ray; 2.38 A; A=28-294.
DR   PDB; 9IO6; X-ray; 2.07 A; A/B=28-294.
DR   PDB; 9IO7; X-ray; 2.40 A; A=28-294.
DR   PDB; 9IOW; X-ray; 2.40 A; A=28-294.
DR   PDB; 9IVL; X-ray; 1.40 A; A=28-294.
DR   PDB; 9JNA; X-ray; 2.40 A; A/B=28-294.
DR   PDB; 9JNB; X-ray; 2.20 A; A=28-294.
DR   PDB; 9JNC; X-ray; 2.57 A; A/B=28-294.
DR   PDB; 9JND; X-ray; 2.30 A; A/B=28-294.
DR   PDB; 9JNE; X-ray; 2.50 A; A/B=28-294.
DR   PDB; 9JNF; X-ray; 2.32 A; A/B=28-294.
DR   PDB; 9JNG; X-ray; 2.26 A; A/B=28-294.
DR   PDB; 9UJ5; X-ray; 2.30 A; A/B=28-294.
DR   PDB; 9UJ6; X-ray; 2.00 A; A/B=28-294.
DR   PDB; 9UJ7; X-ray; 2.20 A; A/B=28-294.
DR   PDB; 9UJ8; X-ray; 2.10 A; A=28-294.
DR   PDB; 9UJ9; X-ray; 2.40 A; A/B=28-294.
DR   PDB; 9UJA; X-ray; 2.20 A; A=28-294.
DR   PDB; 9UJB; X-ray; 2.10 A; A/B=28-294.
DR   PDB; 9UJC; X-ray; 2.00 A; A=28-294.
DR   PDB; 9V49; X-ray; 2.20 A; A/B=28-294.
DR   PDB; 9V4A; X-ray; 2.40 A; A=28-294.
DR   PDB; 9VIU; X-ray; 2.80 A; A/B=28-294.
DR   PDB; 9VXS; X-ray; 2.50 A; A/B=28-294.
DR   PDB; 9W7N; X-ray; 2.00 A; A/B=28-294.
DR   PDB; 9W7O; X-ray; 1.93 A; A/B=28-294.
DR   PDB; 9W7P; X-ray; 2.20 A; A/B=28-294.
DR   AlphaFoldDB; P52682; -.
DR   SMR; P52682; -.
DR   CARD; ARO:3002382; SME-4; ARO:0001004; antibiotic inactivation.
DR   MEROPS; S11.A01; -.
DR   KEGG; ag:CAA82281; -.
DR   PATRIC; fig|615.109.peg.3851; -.
DR   SABIO-RK; P52682; -.
DR   EvolutionaryTrace; Q54488; -.
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; IPR058220; KPC-2/SME-1-like.
DR   InterPro; IPR058198; SME-1.
DR   NCBIfam; NF033103; bla_class_A; 1.
DR   NCBIfam; NF012142; blaSME; 1.
DR   NCBIfam; NF000538; classA_carba; 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.
PE   1: Evidence at protein level;
KW   3D-structure; Antibiotic resistance; Direct protein sequencing;
KW   Disulfide bond; Hydrolase; Signal.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000269|PubMed:8092824"
FT   CHAIN           28..294
FT                   /note="Beta-lactamase SME-1"
FT                   /id="PRO_0000017001"
FT   ACT_SITE        73
FT                   /note="Nucleophile; acyl-ester intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:P62593"
FT   ACT_SITE        76
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P62593"
FT   ACT_SITE        133
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P62593"
FT   ACT_SITE        170
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P62593"
FT   BINDING         73
FT                   /ligand="a beta-lactam"
FT                   /ligand_id="ChEBI:CHEBI:35627"
FT                   /evidence="ECO:0000250|UniProtKB:Q9F663"
FT   BINDING         76
FT                   /ligand="a beta-lactam"
FT                   /ligand_id="ChEBI:CHEBI:35627"
FT                   /evidence="ECO:0000250|UniProtKB:Q9F663"
FT   BINDING         133
FT                   /ligand="a beta-lactam"
FT                   /ligand_id="ChEBI:CHEBI:35627"
FT                   /evidence="ECO:0000250|UniProtKB:Q9F663"
FT   BINDING         135
FT                   /ligand="a beta-lactam"
FT                   /ligand_id="ChEBI:CHEBI:35627"
FT                   /evidence="ECO:0000250|UniProtKB:Q9F663"
FT   BINDING         239
FT                   /ligand="a beta-lactam"
FT                   /ligand_id="ChEBI:CHEBI:35627"
FT                   /evidence="ECO:0000250|UniProtKB:Q9F663"
FT   DISULFID        72..242
FT                   /evidence="ECO:0000269|PubMed:11807251,
FT                   ECO:0007744|PDB:1DY6"
FT   MUTAGEN         72
FT                   /note="C->A: Abolishes resistance to imipenem, amoxicillin,
FT                   ticarcillin, cefoxitin and aztreonam in the JM109 strain
FT                   E.coli."
FT                   /evidence="ECO:0000269|PubMed:11807251"
FT   MUTAGEN         207
FT                   /note="V->E: Similar catalytic efficiency to wild-type with
FT                   respect to penicillins, cephalosporins and carbapenems."
FT                   /evidence="ECO:0000269|PubMed:11036019"
FT   CONFLICT        245
FT                   /note="Y -> I (in Ref. 1;
FT                   AAB03414/AEJ79644/AGZ03855/AHA49908)"
FT                   /evidence="ECO:0000305"
FT   HELIX           33..44
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          46..54
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   TURN            55..58
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          59..64
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           72..75
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           76..88
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           103..106
FT                   /evidence="ECO:0007829|PDB:9IL7"
FT   HELIX           110..114
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   TURN            115..118
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           122..131
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           135..141
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           142..146
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           148..158
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   TURN            170..175
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          182..185
FT                   /evidence="ECO:0007829|PDB:9V49"
FT   HELIX           187..198
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          200..203
FT                   /evidence="ECO:0007829|PDB:9W7O"
FT   HELIX           207..216
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   TURN            222..224
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           225..228
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          233..241
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          248..255
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   STRAND          257..259
FT                   /evidence="ECO:0007829|PDB:9UJC"
FT   STRAND          262..269
FT                   /evidence="ECO:0007829|PDB:9IVL"
FT   HELIX           279..293
FT                   /evidence="ECO:0007829|PDB:9IVL"
SQ   SEQUENCE   294 AA;  32247 MW;  C326C0DC65293094 CRC64;
     MSNKVNFKTA SFLFSVCLAL SAFNAHANKS DAAAKQIKKL EEDFDGRIGV FAIDTGSGNT
     FGYRSDERFP LCSSFKGFLA AAVLERVQQK KLDINQKVKY ESRDLEYHSP ITTKYKGSGM
     TLGDMASAAL QYSDNGATNI IMERFLGGPE GMTKFMRSIG DNEFRLDRWE LELNTAIPGD
     KRDTSTPKAV ANSLNKLALG NVLNAKVKAI YQNWLKGNTT GDARIRASVP ADWVVGDKTG
     SCGAYGTAND YAVIWPKNRA PLIVSIYTTR KSKDDKHSDK TIAEASRIAI QAID
//