COAE_MYCTU
ID COAE_MYCTU Reviewed; 407 AA.
AC P9WPA3; L0T8U1; O06148; P63826;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Dephospho-CoA kinase {ECO:0000255|HAMAP-Rule:MF_00376};
DE EC=2.7.1.24 {ECO:0000255|HAMAP-Rule:MF_00376, ECO:0000269|PubMed:19876400, ECO:0000269|PubMed:21264299};
DE AltName: Full=Dephosphocoenzyme A kinase {ECO:0000255|HAMAP-Rule:MF_00376, ECO:0000303|PubMed:19876400};
GN Name=coaE {ECO:0000255|HAMAP-Rule:MF_00376, ECO:0000303|PubMed:19876400};
GN OrderedLocusNames=Rv1631; ORFNames=MTCY01B2.23;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND DOMAIN.
RX PubMed=19876400; DOI=10.1371/journal.pone.0007645;
RA Walia G., Kumar P., Surolia A.;
RT "The role of UPF0157 in the folding of M. tuberculosis dephosphocoenzyme A
RT kinase and the regulation of the latter by CTP.";
RL PLoS ONE 4:E7645-E7645(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-8; LYS-14; ASP-32;
RP LEU-114 AND ARG-140.
RX PubMed=21264299; DOI=10.1371/journal.pone.0015228;
RA Walia G., Gajendar K., Surolia A.;
RT "Identification of critical residues of the mycobacterial dephosphocoenzyme
RT a kinase by site-directed mutagenesis.";
RL PLoS ONE 6:E15228-E15228(2011).
RN [6]
RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF CYS-235 AND CYS-368.
RX PubMed=21731728; DOI=10.1371/journal.pone.0021390;
RA Walia G., Surolia A.;
RT "Insights into the regulatory characteristics of the mycobacterial
RT dephosphocoenzyme A kinase: implications for the universal CoA biosynthesis
RT pathway.";
RL PLoS ONE 6:E21390-E21390(2011).
CC -!- FUNCTION: Catalyzes the phosphorylation of the 3'-hydroxyl group of
CC dephosphocoenzyme A to form coenzyme A (PubMed:19876400,
CC PubMed:21264299). Can also use dATP, with lower efficiency, but cannot
CC use GTP, dGTP or CTP (PubMed:19876400). {ECO:0000269|PubMed:19876400,
CC ECO:0000269|PubMed:21264299}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-dephospho-CoA + ATP = ADP + CoA + H(+);
CC Xref=Rhea:RHEA:18245, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57328, ChEBI:CHEBI:456216;
CC EC=2.7.1.24; Evidence={ECO:0000255|HAMAP-Rule:MF_00376,
CC ECO:0000269|PubMed:19876400, ECO:0000269|PubMed:21264299};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18246;
CC Evidence={ECO:0000269|PubMed:19876400};
CC -!- ACTIVITY REGULATION: Inhibited by CTP (PubMed:19876400,
CC PubMed:21731728). CTP strongly binds the enzyme at a site overlapping
CC that of the leading substrate, dephosphocoenzyme A. Binding of CTP
CC probably prevents interaction with dephosphocoenzyme A and oligomeric
CC transformation to the active form, which limits the catalytic
CC efficiency of the enzyme (PubMed:21731728).
CC {ECO:0000269|PubMed:19876400, ECO:0000269|PubMed:21731728}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=34.9 uM for dephospho-CoA {ECO:0000269|PubMed:19876400};
CC KM=56.8 uM for ATP {ECO:0000269|PubMed:19876400};
CC KM=320 uM for dATP {ECO:0000269|PubMed:19876400};
CC Note=kcat is 1.76 min(-1). {ECO:0000269|PubMed:19876400};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 5/5. {ECO:0000255|HAMAP-Rule:MF_00376,
CC ECO:0000305|PubMed:19876400}.
CC -!- SUBUNIT: Forms monomers and homotrimers. The monomer is the active form
CC and the trimeric form is inactive. Shift from inactive homotrimer to
CC active monomer is induced in the presence of dephosphocoenzyme A. A
CC dynamic equilibrium between the trimeric and monomeric forms regulates
CC the effective concentration of active enzyme.
CC {ECO:0000269|PubMed:21731728}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00376}.
CC -!- DOMAIN: The C-terminal UPF0157 domain is involved in the proper folding
CC of the full length enzyme. {ECO:0000269|PubMed:19876400}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the CoaE family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the UPF0157 (GrpB)
CC family. {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; AL123456; CCP44395.1; -; Genomic_DNA.
DR PIR; E70559; E70559.
DR RefSeq; NP_216147.1; NC_000962.3.
DR RefSeq; WP_003408069.1; NZ_NVQJ01000016.1.
DR AlphaFoldDB; P9WPA3; -.
DR SMR; P9WPA3; -.
DR STRING; 83332.Rv1631; -.
DR PaxDb; P9WPA3; -.
DR DNASU; 885165; -.
DR GeneID; 885165; -.
DR KEGG; mtu:Rv1631; -.
DR TubercuList; Rv1631; -.
DR eggNOG; COG0237; Bacteria.
DR eggNOG; COG2320; Bacteria.
DR OMA; IRVDGWP; -.
DR BRENDA; 2.7.1.24; 3445.
DR UniPathway; UPA00241; UER00356.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0002135; F:CTP binding; IDA:MTBBASE.
DR GO; GO:0032564; F:dATP binding; IDA:MTBBASE.
DR GO; GO:0004140; F:dephospho-CoA kinase activity; IDA:MTBBASE.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IDA:MTBBASE.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.460.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00376; Dephospho_CoA_kinase; 1.
DR InterPro; IPR001977; Depp_CoAkinase.
DR InterPro; IPR007344; GrpB/CoaE.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01121; CoaE; 1.
DR Pfam; PF04229; GrpB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
DR TIGRFAMs; TIGR00152; TIGR00152; 1.
DR PROSITE; PS51219; DPCK; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coenzyme A biosynthesis; Cytoplasm; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..407
FT /note="Dephospho-CoA kinase"
FT /id="PRO_0000172964"
FT DOMAIN 3..204
FT /note="DPCK"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00376"
FT REGION 211..407
FT /note="UPF0157"
FT /evidence="ECO:0000305"
FT BINDING 11..16
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00376"
FT MUTAGEN 8
FT /note="G->A: Does not change either the Km or the kcat of
FT the reaction considerably."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 14
FT /note="K->A: Shows a 50% increase in the Km for ATP and a
FT 19% reduction in kcat."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 32
FT /note="D->A: Does not affect Km for ATP, but shows a 15-
FT fold increase in the Km for dephospho-CoA. Decrease in kcat
FT and strong decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 32
FT /note="D->E: Decreases Km for both ATP and dephospho-CoA.
FT Has minimal effect on kcat."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 32
FT /note="D->N: Does not affect Km for ATP, but shows a 2.5-
FT fold increase in the Km for dephospho-CoA."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 114
FT /note="L->A: Increases Km for both ATP and dephospho-CoA,
FT but increases the enzymatic turnover."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 140
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 140
FT /note="R->K: Almost loss of activity. Shows very poor
FT binding to ATP."
FT /evidence="ECO:0000269|PubMed:21264299"
FT MUTAGEN 235
FT /note="C->S: Does not affect oligomerization."
FT /evidence="ECO:0000269|PubMed:21731728"
FT MUTAGEN 368
FT /note="C->S: Does not affect oligomerization."
FT /evidence="ECO:0000269|PubMed:21731728"
SQ SEQUENCE 407 AA; 44669 MW; 166F7A3052943DD7 CRC64;
MLRIGLTGGI GAGKSLLSTT FSQCGGIVVD GDVLAREVVQ PGTEGLASLV DAFGRDILLA
DGALDRQALA AKAFRDDESR GVLNGIVHPL VARRRSEIIA AVSGDAVVVE DIPLLVESGM
APLFPLVVVV HADVELRVRR LVEQRGMAEA DARARIAAQA SDQQRRAVAD VWLDNSGSPE
DLVRRARDVW NTRVQPFAHN LAQRQIARAP ARLVPADPSW PDQARRIVNR LKIACGHKAL
RVDHIGSTAV SGFPDFLAKD VIDIQVTVES LDVADELAEP LLAAGYPRLE HITQDTEKTD
ARSTVGRYDH TDSAALWHKR VHASADPGRP TNVHLRVHGW PNQQFALLFV DWLAANPGAR
EDYLTVKCDA DRRADGELAR YVTAKEPWFL DAYQRAWEWA DAVHWRP
