AP4A_MYCTU
ID AP4A_MYCTU Reviewed; 195 AA.
AC P9WMK9; L0TA61; O06201; Q7D6W5;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=AP-4-A phosphorylase;
DE EC=2.7.7.53;
DE AltName: Full=ATP adenylyltransferase;
DE AltName: Full=Diadenosine 5',5'''-P1,P4-tetraphosphate phosphorylase;
DE Short=AP,A phosphorylase;
GN OrderedLocusNames=Rv2613c;
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 SEQUENCE REVISION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368430; DOI=10.1099/00221287-148-10-2967;
RA Camus J.-C., Pryor M.J., Medigue C., Cole S.T.;
RT "Re-annotation of the genome sequence of Mycobacterium tuberculosis
RT H37Rv.";
RL Microbiology 148:2967-2973(2002).
RN [3]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBUNIT, SUBSTRATE SPECIFICITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19778616; DOI=10.1016/j.pep.2009.09.010;
RA Mori S., Shibayama K., Wachino J., Arakawa Y.;
RT "Purification and molecular characterization of a novel diadenosine
RT 5',5'''-P(1),P(4)-tetraphosphate phosphorylase from Mycobacterium
RT tuberculosis H37Rv.";
RL Protein Expr. Purif. 69:99-105(2010).
RN [4]
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 [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEX WITH PHOSPHATE, CATALYTIC
RP ACTIVITY, FUNCTION, SUBUNIT, AND MUTAGENESIS OF ASN-139; GLY-146; SER-147
RP AND TRP-160.
RX PubMed=21565198; DOI=10.1016/j.jmb.2011.04.059;
RA Mori S., Shibayama K., Wachino J., Arakawa Y.;
RT "Structural insights into the novel diadenosine 5',5'''-P(1),P(4)-
RT tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.";
RL J. Mol. Biol. 410:93-104(2011).
CC -!- FUNCTION: Catabolizes diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A)
CC into ADP and ATP. It does not catalyze the reverse phosphorolysis
CC reaction. The optimum substrates are dinucleoside polyphosphates
CC containing four or five phosphate residues.
CC {ECO:0000269|PubMed:19778616, ECO:0000269|PubMed:21565198}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP + ATP + H(+) = P(1),P(4)-bis(5'-adenosyl) tetraphosphate +
CC phosphate; Xref=Rhea:RHEA:16577, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58141,
CC ChEBI:CHEBI:456216; EC=2.7.7.53;
CC Evidence={ECO:0000269|PubMed:21565198};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:19778616};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:19778616};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:19778616};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19778616};
CC Note=Binds 1 divalent metal ion per subunit. Mn(2+) is the most
CC efficient metal, but can also use Co(2+), Ca(2+) and Mg(2+).
CC {ECO:0000269|PubMed:19778616};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 mM for Ap4A (at 37 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:19778616};
CC KM=0.94 mM for phosphate (at 37 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:19778616};
CC Vmax=21.87 umol/min/mg enzyme toward Ap4A(at 37 degrees Celsius and
CC pH 7.6) {ECO:0000269|PubMed:19778616};
CC Vmax=26.96 umol/min/mg enzyme toward phosphate (at 37 degrees Celsius
CC and pH 7.6) {ECO:0000269|PubMed:19778616};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:19778616};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius. The activity completely
CC disappears after treatment at 65 degrees Celsius for 10 min.
CC {ECO:0000269|PubMed:19778616};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:19778616,
CC ECO:0000269|PubMed:21565198}.
CC -!- MISCELLANEOUS: Rv2613c is a unique Ap4A phosphorylase with a primary
CC structure homologous to that of Ap4A hydrolase rather than typical Ap4A
CC phosphorylases. Was identified as a high-confidence drug target.
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DR EMBL; AL123456; CCP45410.1; -; Genomic_DNA.
DR PIR; D70571; D70571.
DR RefSeq; NP_217129.1; NC_000962.3.
DR RefSeq; WP_003413484.1; NZ_NVQJ01000023.1.
DR PDB; 3ANO; X-ray; 1.89 A; A/B=1-195.
DR PDB; 3WO5; X-ray; 2.79 A; A/B=1-195.
DR PDBsum; 3ANO; -.
DR PDBsum; 3WO5; -.
DR AlphaFoldDB; P9WMK9; -.
DR SMR; P9WMK9; -.
DR STRING; 83332.Rv2613c; -.
DR BindingDB; P9WMK9; -.
DR PaxDb; P9WMK9; -.
DR DNASU; 888193; -.
DR GeneID; 45426616; -.
DR GeneID; 888193; -.
DR KEGG; mtu:Rv2613c; -.
DR TubercuList; Rv2613c; -.
DR eggNOG; COG0537; Bacteria.
DR OMA; YNPGHVM; -.
DR PhylomeDB; P9WMK9; -.
DR BRENDA; 2.7.7.53; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003877; F:ATP adenylyltransferase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008796; F:bis(5'-nucleosyl)-tetraphosphatase activity; IDA:UniProtKB.
DR GO; GO:0015967; P:diadenosine tetraphosphate catabolic process; IDA:MTBBASE.
DR CDD; cd01275; FHIT; 1.
DR Gene3D; 3.30.428.10; -; 1.
DR InterPro; IPR039383; FHIT.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR Pfam; PF01230; HIT; 1.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS51084; HIT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; Transferase.
FT CHAIN 1..195
FT /note="AP-4-A phosphorylase"
FT /id="PRO_0000393106"
FT DOMAIN 57..166
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 151..155
FT /note="Histidine triad motif"
FT ACT_SITE 153
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250"
FT MUTAGEN 139
FT /note="N->A,Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:21565198"
FT MUTAGEN 146
FT /note="G->Q: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:21565198"
FT MUTAGEN 147
FT /note="S->A,T: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:21565198"
FT MUTAGEN 160
FT /note="W->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:21565198"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:3WO5"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:3ANO"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:3ANO"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:3ANO"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 108..128
FT /evidence="ECO:0007829|PDB:3ANO"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:3ANO"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:3ANO"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3ANO"
FT HELIX 178..192
FT /evidence="ECO:0007829|PDB:3ANO"
SQ SEQUENCE 195 AA; 21869 MW; 36516FCE8B05D77B CRC64;
MSDEDRTDRA TEDHTIFDRG VGQRDQLQRL WTPYRMNYLA EAPVKRDPNS SASPAQPFTE
IPQLSDEEGL VVARGKLVYA VLNLYPYNPG HLMVVPYRRV SELEDLTDLE SAELMAFTQK
AIRVIKNVSR PHGFNVGLNL GTSAGGSLAE HLHVHVVPRW GGDANFITII GGSKVIPQLL
RDTRRLLATE WARQP
