ID FADE5_MYCS2 Reviewed; 611 AA. AC Q3L887; A0QPI1; I7FWC0; DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2005, sequence version 1. DT 02-JUN-2021, entry version 111. DE RecName: Full=Broad-specificity linear acyl-CoA dehydrogenase FadE5 {ECO:0000305}; DE AltName: Full=Long-chain-acyl-CoA dehydrogenase {ECO:0000305}; DE EC=1.3.8.8 {ECO:0000269|PubMed:32601219}; DE AltName: Full=Medium-chain-acyl-CoA dehydrogenase {ECO:0000305}; DE EC=1.3.8.7 {ECO:0000269|PubMed:32601219}; DE AltName: Full=Short-chain-acyl-CoA dehydrogenase {ECO:0000305}; DE EC=1.3.8.1 {ECO:0000269|PubMed:32601219}; GN Name=fadE5 {ECO:0000303|PubMed:32601219}; GN OrderedLocusNames=MSMEG_0406 {ECO:0000312|EMBL:ABK75628.1}, GN MSMEI_0396 {ECO:0000312|EMBL:AFP36877.1}; OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium OS smegmatis). OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; OC Mycolicibacterium. OX NCBI_TaxID=246196; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 700084 / mc(2)155; RX PubMed=16194230; DOI=10.1111/j.1365-2958.2005.04847.x; RA Sonden B., Kocincova D., Deshayes C., Euphrasie D., Rhayat L., Laval F., RA Frehel C., Daffe M., Etienne G., Reyrat J.M.; RT "Gap, a mycobacterial specific integral membrane protein, is required for RT glycolipid transport to the cell surface."; RL Mol. Microbiol. 58:426-440(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700084 / mc(2)155; RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C., RA Fraser C.M.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700084 / mc(2)155; RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20; RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C., RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.; RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic RT mutations or sequencing errors?"; RL Genome Biol. 8:R20.1-R20.9(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700084 / mc(2)155; RX PubMed=18955433; DOI=10.1101/gr.081901.108; RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M., RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.; RT "Ortho-proteogenomics: multiple proteomes investigation through orthology RT and a new MS-based protocol."; RL Genome Res. 19:128-135(2009). RN [5] {ECO:0007744|PDB:6KPT, ECO:0007744|PDB:6KRI, ECO:0007744|PDB:6KS9, ECO:0007744|PDB:6KSA, ECO:0007744|PDB:6KSB, ECO:0007744|PDB:6LPY, ECO:0007744|PDB:6LQ0, ECO:0007744|PDB:6LQ1, ECO:0007744|PDB:6LQ2, ECO:0007744|PDB:6LQ3, ECO:0007744|PDB:6LQ4} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF WILD-TYPE IN COMPLEX WITH FAD AND RP MUTANT ALA-447 IN COMPLEXES WITH FAD AND LINEAR ACYL-COA SUBSTRATES, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, RP PATHWAY, SUBUNIT, DISRUPTION PHENOTYPE, ACTIVE SITE, AND MUTAGENESIS OF RP GLU-447. RC STRAIN=ATCC 700084 / mc(2)155; RX PubMed=32601219; DOI=10.1073/pnas.2002835117; RA Chen X., Chen J., Yan B., Zhang W., Guddat L.W., Liu X., Rao Z.; RT "Structural basis for the broad substrate specificity of two acyl-CoA RT dehydrogenases FadE5 from mycobacteria."; RL Proc. Natl. Acad. Sci. U.S.A. 117:16324-16332(2020). CC -!- FUNCTION: Acyl-CoA dehydrogenase that exhibits broad specificity for CC linear acyl-CoA substrates, with a preference for long-chain CC substrates. {ECO:0000269|PubMed:32601219}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a long-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized CC [electron-transfer flavoprotein] = a long-chain (2E)-enoyl-CoA + CC reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:17721, CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:83721, CC ChEBI:CHEBI:83727; EC=1.3.8.8; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a medium-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized CC [electron-transfer flavoprotein] = a medium-chain trans-(2E)-enoyl- CC CoA + reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:14477, CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:83723, CC ChEBI:CHEBI:83726; EC=1.3.8.7; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a short-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized CC [electron-transfer flavoprotein] = a short-chain (2E)-enoyl-CoA + CC reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:47196, CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:87487, CC ChEBI:CHEBI:87488; EC=1.3.8.1; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + octadecanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:47240, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57394, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:71412; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hexadecanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:43448, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57692, CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61526; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dodecanoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E)-dodecenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:47296, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=decanoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:48176, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:61406, ChEBI:CHEBI:61430; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hexanoyl-CoA + oxidized [electron-transfer CC flavoprotein] = (2E)-hexenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:43464, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, CC ChEBI:CHEBI:62077, ChEBI:CHEBI:62620; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- CATALYTIC ACTIVITY: CC Reaction=butanoyl-CoA + H(+) + oxidized [electron-transfer CC flavoprotein] = (2E)-butenoyl-CoA + reduced [electron-transfer CC flavoprotein]; Xref=Rhea:RHEA:24004, Rhea:RHEA-COMP:10685, Rhea:RHEA- CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57332, ChEBI:CHEBI:57371, CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; CC Evidence={ECO:0000269|PubMed:32601219}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000305|PubMed:32601219}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=285.9 uM for butanoyl-CoA {ECO:0000269|PubMed:32601219}; CC Note=kcat is 0.53 sec(-1) with butanoyl-CoA as substrate. CC {ECO:0000269|PubMed:32601219}; CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. CC {ECO:0000305|PubMed:32601219}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32601219}. CC -!- DISRUPTION PHENOTYPE: Disruption of the gene does not affect the growth CC rate, but mutant shows decreased resistance to ethambutol and CC streptomycin. {ECO:0000269|PubMed:32601219}. CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase 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; AY439015; AAU04876.1; -; Genomic_DNA. DR EMBL; CP000480; ABK75628.1; -; Genomic_DNA. DR EMBL; CP001663; AFP36877.1; -; Genomic_DNA. DR RefSeq; WP_011726920.1; NZ_SIJM01000040.1. DR RefSeq; YP_884819.1; NC_008596.1. DR PDB; 6KPT; X-ray; 1.96 A; A/B=1-611. DR PDB; 6KRI; X-ray; 1.60 A; A/B=1-611. DR PDB; 6KS9; X-ray; 2.00 A; A/B=1-611. DR PDB; 6KSA; X-ray; 1.77 A; A/B=1-611. DR PDB; 6KSB; X-ray; 1.97 A; A/B=1-611. DR PDB; 6LPY; X-ray; 1.90 A; A/B=1-611. DR PDB; 6LQ0; X-ray; 2.20 A; A/B=1-611. DR PDB; 6LQ1; X-ray; 2.80 A; A/B=1-611. DR PDB; 6LQ2; X-ray; 1.90 A; A/B=1-611. DR PDB; 6LQ3; X-ray; 2.50 A; A/B=1-611. DR PDB; 6LQ4; X-ray; 2.40 A; A/B=1-611. DR PDB; 6LQ5; X-ray; 1.90 A; A/B=1-611. DR PDB; 6LQ6; X-ray; 2.00 A; A/B=1-611. DR PDB; 6LQ7; X-ray; 1.90 A; A/B=1-611. DR PDBsum; 6KPT; -. DR PDBsum; 6KRI; -. DR PDBsum; 6KS9; -. DR PDBsum; 6KSA; -. DR PDBsum; 6KSB; -. DR PDBsum; 6LPY; -. DR PDBsum; 6LQ0; -. DR PDBsum; 6LQ1; -. DR PDBsum; 6LQ2; -. DR PDBsum; 6LQ3; -. DR PDBsum; 6LQ4; -. DR PDBsum; 6LQ5; -. DR PDBsum; 6LQ6; -. DR PDBsum; 6LQ7; -. DR SMR; Q3L887; -. DR STRING; 246196.MSMEI_0396; -. DR PRIDE; Q3L887; -. DR EnsemblBacteria; ABK75628; ABK75628; MSMEG_0406. DR EnsemblBacteria; AFP36877; AFP36877; MSMEI_0396. DR GeneID; 45741997; -. DR KEGG; msg:MSMEI_0396; -. DR KEGG; msm:MSMEG_0406; -. DR PATRIC; fig|246196.19.peg.402; -. DR eggNOG; COG1960; Bacteria. DR OMA; IEHARMM; -. DR OrthoDB; 357522at2; -. DR BioCyc; MSME246196:G1H7P-414-MONOMER; -. DR UniPathway; UPA00199; -. DR Proteomes; UP000000757; Chromosome. DR Proteomes; UP000006158; Chromosome. DR GO; GO:0004085; F:butyryl-CoA dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule. DR GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway. DR InterPro; IPR025878; Acyl-CoA_dh-like_C_dom. DR InterPro; IPR020953; Acyl-CoA_DH_N_bac. DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_cen-dom. DR InterPro; IPR036250; AcylCo_DH-like_C. DR InterPro; IPR009075; AcylCo_DH/oxidase_C. DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom. DR Pfam; PF00441; Acyl-CoA_dh_1; 1. DR Pfam; PF12806; Acyl-CoA_dh_C; 1. DR Pfam; PF02770; Acyl-CoA_dh_M; 1. DR Pfam; PF12418; AcylCoA_DH_N; 1. DR SUPFAM; SSF47203; SSF47203; 1. DR SUPFAM; SSF56645; SSF56645; 1. PE 1: Evidence at protein level; KW 3D-structure; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; KW Oxidoreductase; Reference proteome. FT CHAIN 1..611 FT /note="Broad-specificity linear acyl-CoA dehydrogenase FT FadE5" FT /id="PRO_0000452497" FT NP_BIND 162..165 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT NP_BIND 420..424 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT REGION 224..225 FT /note="A 2,3-saturated acyl-CoA binding" FT /evidence="ECO:0000269|PubMed:32601219" FT REGION 460..461 FT /note="A 2,3-saturated acyl-CoA binding" FT /evidence="ECO:0000269|PubMed:32601219" FT ACT_SITE 447 FT /note="Proton acceptor" FT /evidence="ECO:0000305|PubMed:32601219" FT BINDING 171 FT /note="A 2,3-saturated acyl-CoA" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 171 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 198 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 301 FT /note="A 2,3-saturated acyl-CoA" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 326 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 338 FT /note="A 2,3-saturated acyl-CoA" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 447 FT /note="A 2,3-saturated acyl-CoA" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 449 FT /note="FAD" FT /evidence="ECO:0000269|PubMed:32601219" FT BINDING 456 FT /note="A 2,3-saturated acyl-CoA" FT /evidence="ECO:0000269|PubMed:32601219" FT MUTAGEN 447 FT /note="E->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:32601219" SQ SEQUENCE 611 AA; 66532 MW; 41D1ABFE887E0206 CRC64; MSHYKSNVRD QVFNLFEVFG VDKVLGADKF SDLDADTARE MLTEIARLAE GPIAESFVEG DRNPPVFDPE THTVTLPEGF KKSMRALFDG GWDKVGLAEH LGGIPMPRAL QWALIEHILG ANPAAYMYAM GPGMSEIFYN NGTDEQKKWA TIAAERGWGA TMVLTEPDAG SDVGAGRTKA VQQPDGTWHI EGVKRFITSA DSDDLFENIM HLVLARPEGA GPGTKGLSLF FVPKFHFDHE TGEIGERNGV FVTNVEHKMG LKVSATCELS LGQHGIPAVG WLVGEVHNGI AQMFDVIEQA RMMVGTKAIA TLSTGYLNAL EYAKERVQGA DMTQMTDKTA PRVTITHHPD VRRSLMTQKA YAEGLRAIYL YTATFQDAEV AQAVHGVDGD LAARVNDLLL PIVKGFGSET AYAKLTESLQ TLGGSGFLQD YPIEQYIRDS KIDSLYEGTT AIQAQDFFFR KIIRDKGQAL AYVAGEIEQF IKNENGNGRL KTERELLATA LADVQGMAAS LTGYLMAAQE DAASIYKVGL GSVRFLMAVG DLLSGWLLAR QAAVAIEKLD AGATGADKSF YEGKIAAASF FAKNMLPLLT STRQIIENLD NDVMELDEAA F //