COABC_MYCS2
ID COABC_MYCS2 Reviewed; 414 AA.
AC A0QWT2; I7G171;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Coenzyme A biosynthesis bifunctional protein CoaBC {ECO:0000255|HAMAP-Rule:MF_02225};
DE AltName: Full=DNA/pantothenate metabolism flavoprotein {ECO:0000255|HAMAP-Rule:MF_02225};
DE AltName: Full=Phosphopantothenoylcysteine synthetase/decarboxylase {ECO:0000255|HAMAP-Rule:MF_02225};
DE Short=PPCS-PPCDC {ECO:0000255|HAMAP-Rule:MF_02225};
DE Includes:
DE RecName: Full=Phosphopantothenoylcysteine decarboxylase {ECO:0000255|HAMAP-Rule:MF_02225};
DE Short=PPC decarboxylase {ECO:0000255|HAMAP-Rule:MF_02225};
DE Short=PPC-DC {ECO:0000255|HAMAP-Rule:MF_02225};
DE EC=4.1.1.36 {ECO:0000255|HAMAP-Rule:MF_02225};
DE AltName: Full=CoaC {ECO:0000255|HAMAP-Rule:MF_02225};
DE Includes:
DE RecName: Full=Phosphopantothenate--cysteine ligase {ECO:0000255|HAMAP-Rule:MF_02225};
DE EC=6.3.2.5 {ECO:0000255|HAMAP-Rule:MF_02225};
DE AltName: Full=CoaB {ECO:0000255|HAMAP-Rule:MF_02225};
DE AltName: Full=Phosphopantothenoylcysteine synthetase {ECO:0000255|HAMAP-Rule:MF_02225};
DE Short=PPC synthetase {ECO:0000255|HAMAP-Rule:MF_02225};
DE Short=PPC-S {ECO:0000255|HAMAP-Rule:MF_02225};
GN Name=coaBC {ECO:0000255|HAMAP-Rule:MF_02225};
GN OrderedLocusNames=MSMEG_3054 {ECO:0000312|EMBL:ABK75458.1},
GN MSMEI_2978 {ECO:0000312|EMBL:AFP39442.1};
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 [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 [2]
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 [3]
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 [4] {ECO:0007744|PDB:4QJI}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 186-414 IN COMPLEX WITH CTP.
RA Dranow D.M., Abendroth J., Wernimont A.K., Edwards T.E., Lorimer D.;
RT "Crystal structure of the C-terminal CTP-binding domain of a
RT phosphopantothenoylcysteine decarboxylase/phosphopantothenate-cysteine
RT ligase with bound CTP from Mycobacterium smegmatis.";
RL Submitted (JUN-2014) to the PDB data bank.
RN [5] {ECO:0007744|PDB:6TH2, ECO:0007744|PDB:6THC}
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 186-414 IN COMPLEX WITH CTP AND
RP INHIBITOR, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=33420031; DOI=10.1038/s41467-020-20224-x;
RA Mendes V., Green S.R., Evans J.C., Hess J., Blaszczyk M., Spry C.,
RA Bryant O., Cory-Wright J., Chan D.S., Torres P.H.M., Wang Z., Nahiyaan N.,
RA O'Neill S., Damerow S., Post J., Bayliss T., Lynch S.L., Coyne A.G.,
RA Ray P.C., Abell C., Rhee K.Y., Boshoff H.I.M., Barry C.E. III, Mizrahi V.,
RA Wyatt P.G., Blundell T.L.;
RT "Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric
RT site.";
RL Nat. Commun. 12:143-143(2021).
CC -!- FUNCTION: Catalyzes two sequential steps in the biosynthesis of
CC coenzyme A. In the first step cysteine is conjugated to 4'-
CC phosphopantothenate to form 4-phosphopantothenoylcysteine. In the
CC second step the latter compound is decarboxylated to form 4'-
CC phosphopantotheine. {ECO:0000255|HAMAP-Rule:MF_02225}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + N-[(R)-4-phosphopantothenoyl]-L-cysteine = (R)-4'-
CC phosphopantetheine + CO2; Xref=Rhea:RHEA:16793, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:59458, ChEBI:CHEBI:61723; EC=4.1.1.36;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02225};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-4'-phosphopantothenate + CTP + L-cysteine = CMP +
CC diphosphate + H(+) + N-[(R)-4-phosphopantothenoyl]-L-cysteine;
CC Xref=Rhea:RHEA:19397, ChEBI:CHEBI:10986, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:35235, ChEBI:CHEBI:37563,
CC ChEBI:CHEBI:59458, ChEBI:CHEBI:60377; EC=6.3.2.5;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02225};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02225};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02225};
CC Note=Binds 1 FMN per subunit. {ECO:0000255|HAMAP-Rule:MF_02225};
CC -!- ACTIVITY REGULATION: Two related chemical scaffolds that potently
CC inhibit the activity of the CoaB moiety of CoaBC through a cryptic
CC allosteric site that sits in the dimer interface region of the CoaB
CC enzyme were identified. {ECO:0000269|PubMed:33420031}.
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 2/5. {ECO:0000255|HAMAP-Rule:MF_02225}.
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 3/5. {ECO:0000255|HAMAP-Rule:MF_02225}.
CC -!- SUBUNIT: Homododecamer. {ECO:0000269|PubMed:33420031}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the HFCD (homo-
CC oligomeric flavin containing Cys decarboxylase) superfamily.
CC {ECO:0000255|HAMAP-Rule:MF_02225}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the PPC synthetase
CC family. {ECO:0000255|HAMAP-Rule:MF_02225}.
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DR EMBL; CP000480; ABK75458.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP39442.1; -; Genomic_DNA.
DR RefSeq; WP_011728784.1; NZ_SIJM01000002.1.
DR RefSeq; YP_887370.1; NC_008596.1.
DR PDB; 4QJI; X-ray; 2.65 A; A/B=186-414.
DR PDB; 6TGV; X-ray; 2.50 A; A/B/C/D=1-414.
DR PDB; 6TH2; X-ray; 1.84 A; A/B/C/D=186-414.
DR PDB; 6THC; X-ray; 2.03 A; A/B/C/D=186-414.
DR PDBsum; 4QJI; -.
DR PDBsum; 6TGV; -.
DR PDBsum; 6TH2; -.
DR PDBsum; 6THC; -.
DR AlphaFoldDB; A0QWT2; -.
DR SMR; A0QWT2; -.
DR STRING; 246196.MSMEI_2978; -.
DR EnsemblBacteria; ABK75458; ABK75458; MSMEG_3054.
DR EnsemblBacteria; AFP39442; AFP39442; MSMEI_2978.
DR GeneID; 66734459; -.
DR KEGG; msg:MSMEI_2978; -.
DR KEGG; msm:MSMEG_3054; -.
DR PATRIC; fig|246196.19.peg.3015; -.
DR eggNOG; COG0452; Bacteria.
DR OMA; LDMIVAN; -.
DR OrthoDB; 1346419at2; -.
DR UniPathway; UPA00241; UER00353.
DR UniPathway; UPA00241; UER00354.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0010181; F:FMN binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004632; F:phosphopantothenate--cysteine ligase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004633; F:phosphopantothenoylcysteine decarboxylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0015941; P:pantothenate catabolic process; IEA:InterPro.
DR Gene3D; 3.40.50.10300; -; 1.
DR Gene3D; 3.40.50.1950; -; 1.
DR HAMAP; MF_02225; CoaBC; 1.
DR InterPro; IPR035929; CoaB-like_sf.
DR InterPro; IPR005252; CoaBC.
DR InterPro; IPR007085; DNA/pantothenate-metab_flavo_C.
DR InterPro; IPR036551; Flavin_trans-like.
DR InterPro; IPR003382; Flavoprotein.
DR Pfam; PF04127; DFP; 1.
DR Pfam; PF02441; Flavoprotein; 1.
DR SUPFAM; SSF102645; SSF102645; 1.
DR SUPFAM; SSF52507; SSF52507; 1.
DR TIGRFAMs; TIGR00521; coaBC_dfp; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Decarboxylase; Flavoprotein; FMN; Ligase; Lyase; Magnesium;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..414
FT /note="Coenzyme A biosynthesis bifunctional protein CoaBC"
FT /id="PRO_0000453018"
FT REGION 1..191
FT /note="Phosphopantothenoylcysteine decarboxylase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225"
FT REGION 192..414
FT /note="Phosphopantothenate--cysteine ligase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225"
FT BINDING 275..277
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2,
FT ECO:0007744|PDB:6THC"
FT BINDING 281
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225,
FT ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2"
FT BINDING 291
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225,
FT ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6THC"
FT BINDING 293..294
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000269|PubMed:33420031,
FT ECO:0007744|PDB:6TH2, ECO:0007744|PDB:6THC"
FT BINDING 308..311
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2,
FT ECO:0007744|PDB:6THC"
FT BINDING 332
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225,
FT ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2,
FT ECO:0007744|PDB:6THC"
FT BINDING 350
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225,
FT ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2,
FT ECO:0007744|PDB:6THC"
FT BINDING 354
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02225,
FT ECO:0000269|PubMed:33420031, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4QJI, ECO:0007744|PDB:6TH2,
FT ECO:0007744|PDB:6THC"
FT STRAND 6..11
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 17..29
FT /evidence="ECO:0007829|PDB:6TGV"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:6TGV"
FT TURN 63..66
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:6TGV"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:6TGV"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 89..97
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 103..110
FT /evidence="ECO:0007829|PDB:6TGV"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 129..141
FT /evidence="ECO:0007829|PDB:6TGV"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:6TGV"
FT TURN 186..189
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 201..211
FT /evidence="ECO:0007829|PDB:6TH2"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6TH2"
FT HELIX 256..266
FT /evidence="ECO:0007829|PDB:6TH2"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:6THC"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:6TH2"
FT HELIX 310..319
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 328..335
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:6TGV"
FT HELIX 343..354
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 357..363
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:6TH2"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:6TH2"
FT HELIX 394..411
FT /evidence="ECO:0007829|PDB:6TH2"
SQ SEQUENCE 414 AA; 43152 MW; F17FFB968FA8E593 CRC64;
MSARKRIVVG VAGGIAAYKA CTVVRQLTEA GHSVRVVPTE SALRFVGAAT FEALSGNPVH
TGVFTDVHEV QHVRIGQQAD LVVIAPATAD LLARAVAGRA DDLLTATLLT ARCPVLFAPA
MHTEMWLHPA TVDNVATLRR RGAVVLEPAS GRLTGADSGP GRLPEAEEIT TLAQLLLERA
DALPYDMAGV KALVTAGGTR EPLDPVRFIG NRSSGKQGYA VARVLAQRGA DVTLIAGNTA
GLIDPAGVEM VHIGSATQLR DAVSKHAPDA NVLVMAAAVA DFRPAHVAAA KIKKGASEPS
SIDLVRNDDV LAGAVRARAD GQLPNMRAIV GFAAETGDAN GDVLFHARAK LERKGCDLLV
VNAVGENRAF EVDHNDGWLL SADGTESALE HGSKTLMATR IVDSIAAFLK SQDG
