COAD_MYCTU
ID COAD_MYCTU Reviewed; 161 AA.
AC P9WPA5; L0TCR8; O08023; P0A530; Q50452;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Phosphopantetheine adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000303|PubMed:15322293, ECO:0000303|Ref.5};
DE EC=2.7.7.3 {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000269|PubMed:20851704, ECO:0000269|Ref.5};
DE AltName: Full=Dephospho-CoA pyrophosphorylase {ECO:0000255|HAMAP-Rule:MF_00151};
DE AltName: Full=Pantetheine-phosphate adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_00151};
DE Short=PPAT {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000303|PubMed:15322293, ECO:0000303|Ref.5};
GN Name=coaD {ECO:0000255|HAMAP-Rule:MF_00151};
GN Synonyms=kdtB {ECO:0000303|Ref.5}; OrderedLocusNames=Rv2965c;
GN ORFNames=MTCY349.22, u0002e;
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 [GENOMIC DNA].
RA Smith D.R., Robison K.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [4]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 1-157, AND SUBUNIT.
RX PubMed=15322293; DOI=10.1110/ps.04816904;
RA Morris V.K., Izard T.;
RT "Substrate-induced asymmetry and channel closure revealed by the apoenzyme
RT structure of Mycobacterium tuberculosis phosphopantetheine
RT adenylyltransferase.";
RL Protein Sci. 13:2547-2552(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH THE NATURAL
RP INHIBITOR COENZYME A, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND SUBUNIT.
RC STRAIN=H37Rv;
RX DOI=10.1134/S1063774510060234;
RA Timofeev V.I., Smirnova E.A., Chupova L.A., Esipov R.S., Kuranova I.P.;
RT "Preparation of the crystal complex of phosphopantetheine
RT adenylyltransferase from Mycobacterium tuberculosis with Coenzyme A and
RT investigation of its three-dimensional structure at 2.1-A frame
RT resolution.";
RL Crystallogr. Rep. 55:1050-1059(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 1-157 IN COMPLEXES WITH
RP PHOSPHOPANTETHEINE AND A NON-HYDROLYZABLE ATP ANALOG, FUNCTION, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20851704; DOI=10.1016/j.jmb.2010.09.002;
RA Wubben T.J., Mesecar A.D.;
RT "Kinetic, thermodynamic, and structural insight into the mechanism of
RT phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 404:202-219(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 1-157 IN COMPLEX WITH THE NATURAL
RP INHIBITOR COENZYME A, AND ACTIVITY REGULATION.
RX PubMed=21543857; DOI=10.1107/s1744309111010761;
RA Wubben T., Mesecar A.D.;
RT "Structure of Mycobacterium tuberculosis phosphopantetheine
RT adenylyltransferase in complex with the feedback inhibitor CoA reveals only
RT one active-site conformation.";
RL Acta Crystallogr. F 67:541-545(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) IN THE APO FORM AND IN COMPLEX WITH
RP ATP.
RC STRAIN=H37Rv;
RX PubMed=23151631; DOI=10.1107/s0907444912040206;
RA Timofeev V., Smirnova E., Chupova L., Esipov R., Kuranova I.;
RT "X-ray study of the conformational changes in the molecule of
RT phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis
RT during the catalyzed reaction.";
RL Acta Crystallogr. D 68:1660-1670(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 1-157 IN THE APO FORM AND IN
RP COMPLEXES WITH COA AND 3'-DEPHOSPHO-COA.
RX DOI=10.1134/S1063774512010142;
RA Timofeev V.I., Smirnova E.A., Chupova L.A., Esipov R.S., Kuranova I.P.;
RT "Three-dimensional structure of phosphopantetheine adenylyltransferase from
RT Mycobacterium Tuberculosis in the apo form and in complexes with coenzyme A
RT and dephosphocoenzyme A.";
RL Crystallogr. Rep. 57:96-104(2012).
CC -!- FUNCTION: Reversibly transfers an adenylyl group from ATP to 4'-
CC phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate.
CC {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000269|PubMed:20851704,
CC ECO:0000269|Ref.5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-4'-phosphopantetheine + ATP + H(+) = 3'-dephospho-CoA +
CC diphosphate; Xref=Rhea:RHEA:19801, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57328,
CC ChEBI:CHEBI:61723; EC=2.7.7.3; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00151, ECO:0000269|PubMed:20851704, ECO:0000269|Ref.5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00151};
CC -!- ACTIVITY REGULATION: Regulated by Coenzyme A (CoA) through feedback
CC inhibition. {ECO:0000305|PubMed:21543857, ECO:0000305|Ref.5}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.7 uM for 3'-dephospho-CoA {ECO:0000269|PubMed:20851704};
CC Note=kcat is 288.5 min(-1) for the reverse reaction, with diphosphate
CC and 3'-dephospho-CoA as substrates, which is nearly identical to that
CC of the forward reaction fitted to the Hill equation. The enzyme seems
CC to utilize a nonrapid-equilibrium random bi-bi mechanism with a
CC preferred pathway to the ternary complex. A sigmoidal response is
CC observed when ATP was varied at different fixed concentrations of
CC pantetheine 4'-phosphate. Also exhibits nonhyperbolic kinetics when
CC pantetheine 4'-phosphate was varied at a fixed saturating
CC concentration of ATP. {ECO:0000269|PubMed:20851704};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 4/5. {ECO:0000255|HAMAP-Rule:MF_00151}.
CC -!- SUBUNIT: Homohexamer; dimer of trimers. {ECO:0000255|HAMAP-
CC Rule:MF_00151, ECO:0000269|Ref.5, ECO:0000305|PubMed:15322293}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00151}.
CC -!- SIMILARITY: Belongs to the bacterial CoaD family. {ECO:0000255|HAMAP-
CC Rule:MF_00151}.
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DR EMBL; U00024; AAA50946.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45769.1; -; Genomic_DNA.
DR PIR; B70671; B70671.
DR RefSeq; NP_217481.1; NC_000962.3.
DR RefSeq; WP_003414998.1; NZ_NVQJ01000015.1.
DR PDB; 1TFU; X-ray; 1.99 A; A=1-157.
DR PDB; 3LCJ; X-ray; 2.10 A; A=1-161.
DR PDB; 3NBA; X-ray; 2.68 A; A/B/C/D=1-157.
DR PDB; 3NBK; X-ray; 1.58 A; A/B/C/D=1-157.
DR PDB; 3PNB; X-ray; 2.11 A; A/B/C/D=1-157.
DR PDB; 3RBA; X-ray; 1.59 A; A=1-157.
DR PDB; 3RFF; X-ray; 1.76 A; A=1-157.
DR PDB; 3RHS; X-ray; 1.59 A; A=1-157.
DR PDB; 3UC5; X-ray; 1.70 A; A=1-157.
DR PDB; 4E1A; X-ray; 1.62 A; A=1-161.
DR PDB; 4R0N; X-ray; 2.00 A; A/C/E/G/I/K=2-157.
DR PDB; 6G6V; X-ray; 1.94 A; A=1-161.
DR PDB; 6G7S; X-ray; 1.77 A; A=1-161.
DR PDB; 6G7T; X-ray; 1.65 A; A=1-161.
DR PDB; 6G7U; X-ray; 1.84 A; A=1-161.
DR PDB; 6G7V; X-ray; 1.78 A; A=1-161.
DR PDB; 6QMF; X-ray; 1.77 A; A=1-161.
DR PDB; 6QMG; X-ray; 1.65 A; A=1-161.
DR PDB; 6QMI; X-ray; 1.78 A; A=1-161.
DR PDBsum; 1TFU; -.
DR PDBsum; 3LCJ; -.
DR PDBsum; 3NBA; -.
DR PDBsum; 3NBK; -.
DR PDBsum; 3PNB; -.
DR PDBsum; 3RBA; -.
DR PDBsum; 3RFF; -.
DR PDBsum; 3RHS; -.
DR PDBsum; 3UC5; -.
DR PDBsum; 4E1A; -.
DR PDBsum; 4R0N; -.
DR PDBsum; 6G6V; -.
DR PDBsum; 6G7S; -.
DR PDBsum; 6G7T; -.
DR PDBsum; 6G7U; -.
DR PDBsum; 6G7V; -.
DR PDBsum; 6QMF; -.
DR PDBsum; 6QMG; -.
DR PDBsum; 6QMI; -.
DR AlphaFoldDB; P9WPA5; -.
DR SMR; P9WPA5; -.
DR STRING; 83332.Rv2965c; -.
DR iPTMnet; P9WPA5; -.
DR PaxDb; P9WPA5; -.
DR DNASU; 888423; -.
DR GeneID; 45426954; -.
DR GeneID; 888423; -.
DR KEGG; mtu:Rv2965c; -.
DR TubercuList; Rv2965c; -.
DR eggNOG; COG0669; Bacteria.
DR OMA; EFQMALM; -.
DR PhylomeDB; P9WPA5; -.
DR BRENDA; 2.7.7.3; 3445.
DR UniPathway; UPA00241; UER00355.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004595; F:pantetheine-phosphate adenylyltransferase activity; IDA:MTBBASE.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IDA:MTBBASE.
DR GO; GO:0034214; P:protein hexamerization; IDA:MTBBASE.
DR CDD; cd02163; PPAT; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR HAMAP; MF_00151; PPAT_bact; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR001980; PPAT.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR21342:SF1; PTHR21342:SF1; 1.
DR Pfam; PF01467; CTP_transf_like; 1.
DR PRINTS; PR01020; LPSBIOSNTHSS.
DR TIGRFAMs; TIGR01510; coaD_prev_kdtB; 1.
DR TIGRFAMs; TIGR00125; cyt_tran_rel; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Coenzyme A biosynthesis; Cytoplasm;
KW Magnesium; Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..161
FT /note="Phosphopantetheine adenylyltransferase"
FT /id="PRO_0000156242"
FT BINDING 9..10
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:23151631, ECO:0000305|PubMed:20851704,
FT ECO:0007744|PDB:3NBA, ECO:0007744|PDB:3UC5"
FT BINDING 9
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:20851704, ECO:0007744|PDB:3NBK"
FT BINDING 17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:23151631, ECO:0000305|PubMed:20851704,
FT ECO:0007744|PDB:3NBA, ECO:0007744|PDB:3UC5"
FT BINDING 41
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 73
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:20851704, ECO:0007744|PDB:3NBK"
FT BINDING 87
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 88..90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:23151631, ECO:0000305|PubMed:20851704,
FT ECO:0007744|PDB:3NBA, ECO:0007744|PDB:3UC5"
FT BINDING 98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:23151631, ECO:0007744|PDB:3UC5"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20851704,
FT ECO:0007744|PDB:3NBK"
FT BINDING 118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23151631,
FT ECO:0000305|PubMed:20851704, ECO:0007744|PDB:3NBA,
FT ECO:0007744|PDB:3UC5"
FT BINDING 122..128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000269|PubMed:23151631, ECO:0000305|PubMed:20851704,
FT ECO:0007744|PDB:3NBA, ECO:0007744|PDB:3UC5"
FT SITE 17
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 15..27
FT /evidence="ECO:0007829|PDB:3NBK"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:3NBK"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:3RHS"
FT HELIX 47..57
FT /evidence="ECO:0007829|PDB:3NBK"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 73..79
FT /evidence="ECO:0007829|PDB:3NBK"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 95..109
FT /evidence="ECO:0007829|PDB:3NBK"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 127..135
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3NBK"
FT HELIX 146..156
FT /evidence="ECO:0007829|PDB:3NBK"
SQ SEQUENCE 161 AA; 17628 MW; DE9F12E18D0C1721 CRC64;
MTGAVCPGSF DPVTLGHVDI FERAAAQFDE VVVAILVNPA KTGMFDLDER IAMVKESTTH
LPNLRVQVGH GLVVDFVRSC GMTAIVKGLR TGTDFEYELQ MAQMNKHIAG VDTFFVATAP
RYSFVSSSLA KEVAMLGGDV SELLPEPVNR RLRDRLNTER T
