COAD_HELPY
ID COAD_HELPY Reviewed; 157 AA.
AC O26010;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Phosphopantetheine adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000303|PubMed:21527250};
DE EC=2.7.7.3 {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000269|PubMed:24040220};
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:21527250};
GN Name=coaD {ECO:0000255|HAMAP-Rule:MF_00151}; Synonyms=kdtB;
GN OrderedLocusNames=HP_1475;
OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85962;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=9252185; DOI=10.1038/41483;
RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT "The complete genome sequence of the gastric pathogen Helicobacter
RT pylori.";
RL Nature 388:539-547(1997).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=24040220; DOI=10.1371/journal.pone.0074271;
RA Cheng C.S., Jia K.F., Chen T., Chang S.Y., Lin M.S., Yin H.S.;
RT "Experimentally validated novel inhibitors of Helicobacter pylori
RT phosphopantetheine adenylyltransferase discovered by virtual high-
RT throughput screening.";
RL PLoS ONE 8:E74271-E74271(2013).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COENZYME A, SUBUNIT,
RP AND ACTIVITY REGULATION.
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=21527250; DOI=10.1016/j.bbrc.2011.04.058;
RA Cheng C.S., Chen C.H., Luo Y.C., Chen W.T., Chang S.Y., Lyu P.C., Kao M.C.,
RA Yin H.S.;
RT "Crystal structure and biophysical characterisation of Helicobacter pylori
RT phosphopantetheine adenylyltransferase.";
RL Biochem. Biophys. Res. Commun. 408:356-361(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF MUTANT VAL-4/TYR-76, MUTAGENESIS
RP OF 4-ILE--ASN-76, AND ATP-BINDING.
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=22694317; DOI=10.1080/07391102.2012.682213;
RA Cheng C.S., Chen W.T., Chen Y.W., Chen C.H., Luo Y.C., Lyu P.C., Yin H.S.;
RT "Substitution of asparagine 76 by a tyrosine residue induces domain
RT swapping in Helicobacter pylori phosphopantetheine adenylyltransferase.";
RL J. Biomol. Struct. Dyn. 30:488-502(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:24040220}.
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:24040220};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00151};
CC -!- ACTIVITY REGULATION: Tightly binds to CoA, which is presumably a
CC feedback inhibitor (PubMed:21527250). Potently inhibited by D-
CC amethopterin, which simultaneously occupies the 4'-
CC phosphopantetheine- and ATP-binding sites; following treatment with D-
CC amethopterin, H.pylori exhibits morphological characteristics
CC associated with cell death, showing that D-amethopterin displays
CC antimicrobial activity (PubMed:24040220). {ECO:0000269|PubMed:24040220,
CC ECO:0000305|PubMed:21527250}.
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 4/5. {ECO:0000255|HAMAP-Rule:MF_00151}.
CC -!- SUBUNIT: Homohexamer. {ECO:0000255|HAMAP-Rule:MF_00151,
CC ECO:0000269|PubMed:21527250}.
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; AE000511; AAD08514.1; -; Genomic_DNA.
DR PIR; C64704; C64704.
DR RefSeq; NP_208266.1; NC_000915.1.
DR RefSeq; WP_001169234.1; NC_018939.1.
DR PDB; 3NV7; X-ray; 1.75 A; A=1-157.
DR PDB; 3OTW; X-ray; 1.80 A; A/B/C/D/E/F=1-157.
DR PDBsum; 3NV7; -.
DR PDBsum; 3OTW; -.
DR AlphaFoldDB; O26010; -.
DR SMR; O26010; -.
DR STRING; 85962.C694_07635; -.
DR PaxDb; O26010; -.
DR PRIDE; O26010; -.
DR EnsemblBacteria; AAD08514; AAD08514; HP_1475.
DR KEGG; hpy:HP_1475; -.
DR PATRIC; fig|85962.47.peg.1586; -.
DR eggNOG; COG0669; Bacteria.
DR OMA; EFQMALM; -.
DR PhylomeDB; O26010; -.
DR BRENDA; 2.7.7.3; 2604.
DR UniPathway; UPA00241; UER00355.
DR EvolutionaryTrace; O26010; -.
DR Proteomes; UP000000429; 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; IEA:UniProtKB-UniRule.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IEA:UniProtKB-UniRule.
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; ATP-binding; Coenzyme A biosynthesis; Cytoplasm; Magnesium;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT CHAIN 1..157
FT /note="Phosphopantetheine adenylyltransferase"
FT /id="PRO_0000156217"
FT BINDING 10..11
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 10
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000305|PubMed:21527250, ECO:0007744|PDB:3OTW"
FT BINDING 18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 42
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000305|PubMed:21527250, ECO:0007744|PDB:3OTW"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000305|PubMed:21527250, ECO:0007744|PDB:3OTW"
FT BINDING 88
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 89..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151,
FT ECO:0000305|PubMed:21527250, ECO:0007744|PDB:3OTW"
FT BINDING 99
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT BINDING 124..130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT SITE 18
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00151"
FT MUTAGEN 4
FT /note="I->V: Forms a domain-swapped homotetramer; when
FT associated with Y-76."
FT /evidence="ECO:0000269|PubMed:22694317"
FT MUTAGEN 76
FT /note="N->Y: Forms a domain-swapped homotetramer; when
FT associated with V-4."
FT /evidence="ECO:0000269|PubMed:22694317"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 16..26
FT /evidence="ECO:0007829|PDB:3NV7"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 48..59
FT /evidence="ECO:0007829|PDB:3NV7"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 74..80
FT /evidence="ECO:0007829|PDB:3NV7"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:3OTW"
FT HELIX 96..108
FT /evidence="ECO:0007829|PDB:3NV7"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:3OTW"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 129..137
FT /evidence="ECO:0007829|PDB:3NV7"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:3NV7"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:3NV7"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:3NV7"
SQ SEQUENCE 157 AA; 17668 MW; 4250742EAB58E097 CRC64;
MQKIGIYPGT FDPVTNGHID IIHRSSELFE KLIVAVAHSS AKNPMFSLDE RLKMIQLATK
SFKNVECVAF EGLLANLAKE YHCKVLVRGL RVVSDFEYEL QMGYANKSLN HELETLYFMP
TLQNAFISSS IVRSIIAHKG DASHLVPKEI YPLISKA
