KPRS_MYCTU
ID KPRS_MYCTU Reviewed; 326 AA.
AC P9WKE3; L0T8D7; P65232; P96383;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Ribose-phosphate pyrophosphokinase {ECO:0000255|HAMAP-Rule:MF_00583};
DE Short=RPPK {ECO:0000255|HAMAP-Rule:MF_00583};
DE EC=2.7.6.1 {ECO:0000255|HAMAP-Rule:MF_00583, ECO:0000269|PubMed:21045009, ECO:0000269|PubMed:21085589, ECO:0000269|PubMed:22745722};
DE AltName: Full=5-phospho-D-ribosyl alpha-1-diphosphate {ECO:0000255|HAMAP-Rule:MF_00583};
DE AltName: Full=Phosphoribosyl diphosphate synthase {ECO:0000255|HAMAP-Rule:MF_00583};
DE AltName: Full=Phosphoribosyl pyrophosphate synthase {ECO:0000255|HAMAP-Rule:MF_00583, ECO:0000303|PubMed:21085589};
DE Short=P-Rib-PP synthase {ECO:0000255|HAMAP-Rule:MF_00583};
DE Short=PRPP synthase {ECO:0000255|HAMAP-Rule:MF_00583, ECO:0000303|PubMed:21085589};
DE Short=PRPPase {ECO:0000255|HAMAP-Rule:MF_00583, ECO:0000303|PubMed:21085589};
GN Name=prs {ECO:0000255|HAMAP-Rule:MF_00583};
GN Synonyms=prsA {ECO:0000303|PubMed:9634230}; OrderedLocusNames=Rv1017c;
GN ORFNames=MTCY10G2.32;
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 PUPYLATION AT LYS-29, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20066036; DOI=10.1371/journal.pone.0008589;
RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E.,
RA Gygi S.P., Darwin K.H.;
RT "Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 5:E8589-E8589(2010).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, COFACTOR, AND SUBUNIT.
RX PubMed=21085589; DOI=10.1371/journal.pone.0015494;
RA Lucarelli A.P., Buroni S., Pasca M.R., Rizzi M., Cavagnino A.,
RA Valentini G., Riccardi G., Chiarelli L.R.;
RT "Mycobacterium tuberculosis phosphoribosylpyrophosphate synthetase:
RT biochemical features of a crucial enzyme for mycobacterial cell wall
RT biosynthesis.";
RL PLoS ONE 5:E15494-E15494(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP ACTIVITY REGULATION, PATHWAY, AND SUBUNIT.
RX PubMed=21045009; DOI=10.1093/glycob/cwq173;
RA Alderwick L.J., Lloyd G.S., Lloyd A.J., Lovering A.L., Eggeling L.,
RA Besra G.S.;
RT "Biochemical characterization of the Mycobacterium tuberculosis
RT phosphoribosyl-1-pyrophosphate synthetase.";
RL Glycobiology 21:410-425(2011).
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RX PubMed=22745722; DOI=10.1371/journal.pone.0039245;
RA Breda A., Martinelli L.K., Bizarro C.V., Rosado L.A., Borges C.B.,
RA Santos D.S., Basso L.A.;
RT "Wild-type phosphoribosylpyrophosphate synthase (PRS) from Mycobacterium
RT tuberculosis: a bacterial class II PRS?";
RL PLoS ONE 7:E39245-E39245(2012).
RN [7]
RP REVIEW.
RX PubMed=28031352; DOI=10.1128/mmbr.00040-16;
RA Hove-Jensen B., Andersen K.R., Kilstrup M., Martinussen J., Switzer R.L.,
RA Willemoes M.;
RT "Phosphoribosyl diphosphate (PRPP): biosynthesis, enzymology, utilization,
RT and metabolic significance.";
RL Microbiol. Mol. Biol. Rev. 81:E00040-E00040(2017).
CC -!- FUNCTION: Involved in the biosynthesis of the central metabolite
CC phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) and of the
CC decaprenylphosphoryl-arabinose (DPA), an essential precursor for the
CC mycobacterial cell wall biosynthesis. Catalyzes the transfer of
CC pyrophosphoryl group from ATP to 1-hydroxyl of ribose-5-phosphate (Rib-
CC 5-P) to yield phosphoribosyl diphosphate (PRPP) and AMP. It can also
CC use GTP, CTP and UTP as diphosphoryl donors (PubMed:22745722).
CC {ECO:0000269|PubMed:21045009, ECO:0000269|PubMed:21085589,
CC ECO:0000269|PubMed:22745722}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-ribose 5-phosphate = 5-phospho-alpha-D-ribose 1-
CC diphosphate + AMP + H(+); Xref=Rhea:RHEA:15609, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58017, ChEBI:CHEBI:78346,
CC ChEBI:CHEBI:456215; EC=2.7.6.1; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00583, ECO:0000269|PubMed:21045009,
CC ECO:0000269|PubMed:21085589, ECO:0000269|PubMed:22745722};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00583,
CC ECO:0000269|PubMed:21045009, ECO:0000269|PubMed:21085589};
CC Note=Binds 2 Mg(2+) ions per subunit (Potential). Can also use Mn(2+)
CC (PubMed:21085589, PubMed:21045009). {ECO:0000255|HAMAP-Rule:MF_00583,
CC ECO:0000269|PubMed:21045009, ECO:0000269|PubMed:21085589};
CC -!- ACTIVITY REGULATION: Activated by inorganic phosphate, and to a lesser
CC extent by sulfate ions (PubMed:21085589, PubMed:21045009). In addition
CC to form a complex with ATP, Mg(2+) also acts as a cofactor
CC (PubMed:21085589, PubMed:21045009). Strongly inhibited by ADP and GDP
CC through competitive binding at the activation site and at a specific
CC allosteric site (PubMed:21085589, PubMed:21045009, PubMed:22745722).
CC Competitively inhibited by Ca(2+), Cu(2+) and Fe(2+) (PubMed:21085589,
CC PubMed:21045009). {ECO:0000269|PubMed:21045009,
CC ECO:0000269|PubMed:21085589, ECO:0000269|PubMed:22745722}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.2 uM for Rib-5-P {ECO:0000269|PubMed:21045009};
CC KM=14 uM for Rib-5-P {ECO:0000269|PubMed:22745722};
CC KM=25 uM for ATP {ECO:0000269|PubMed:22745722};
CC KM=26 uM for CTP {ECO:0000269|PubMed:22745722};
CC KM=37 uM for GTP {ECO:0000269|PubMed:22745722};
CC KM=52 uM for UTP {ECO:0000269|PubMed:22745722};
CC KM=70 uM for Rib-5-P (without divalent cation)
CC {ECO:0000269|PubMed:21085589};
CC Vmax=601 umol/min/mg enzyme with ATP as substrate
CC {ECO:0000269|PubMed:21045009};
CC Vmax=530 umol/min/mg enzyme with Rib-5-P as substrate
CC {ECO:0000269|PubMed:21045009};
CC Vmax=1.41 umol/min/mg enzyme with Rib-5-P as substrate
CC {ECO:0000269|PubMed:22745722};
CC Vmax=1.12 umol/min/mg enzyme with ATP as substrate
CC {ECO:0000269|PubMed:22745722};
CC Vmax=0.264 umol/min/mg enzyme with UTP as substrate
CC {ECO:0000269|PubMed:22745722};
CC Vmax=0.237 umol/min/mg enzyme with GTP as substrate
CC {ECO:0000269|PubMed:22745722};
CC Vmax=0.237 umol/min/mg enzyme with CTP as substrate
CC {ECO:0000269|PubMed:22745722};
CC Note=kcat is 37 sec(-1) with Rib-5-P as substrate (PubMed:21085589).
CC kcat is 0.83 sec(-1) with Rib-5-P as substrate (PubMed:22745722).
CC kcat is 0.66 sec(-1) with ATP as substrate (PubMed:22745722). kcat is
CC 0.155 sec(-1) with UTP as substrate (PubMed:22745722). kcat is 0.140
CC sec(-1) with GTP as substrate (PubMed:22745722). kcat is 0.065 sec(-
CC 1) with CTP as substrate (PubMed:22745722).
CC {ECO:0000269|PubMed:21085589, ECO:0000269|PubMed:22745722};
CC pH dependence:
CC Optimum pH is close to 8 (PubMed:21085589). Activities at pH 7 and pH
CC 9.5 are 57% and 70% of the maximal activity, respectively
CC (PubMed:21085589, PubMed:21045009). {ECO:0000269|PubMed:21045009,
CC ECO:0000269|PubMed:21085589};
CC Temperature dependence:
CC Thermostable. {ECO:0000269|PubMed:21085589};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose
CC 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from
CC D-ribose 5-phosphate (route I): step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_00583, ECO:0000305|PubMed:21045009}.
CC -!- PATHWAY: Cell wall biogenesis; cell wall polysaccharide biosynthesis.
CC {ECO:0000269|PubMed:21045009}.
CC -!- SUBUNIT: Homohexamer. {ECO:0000269|PubMed:21085589,
CC ECO:0000269|PubMed:22745722, ECO:0000305|PubMed:21045009}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00583}.
CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase family.
CC Class I subfamily. {ECO:0000255|HAMAP-Rule:MF_00583,
CC ECO:0000303|PubMed:28031352}.
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DR EMBL; AL123456; CCP43767.1; -; Genomic_DNA.
DR PIR; D70622; D70622.
DR RefSeq; NP_215533.1; NC_000962.3.
DR RefSeq; WP_003405263.1; NZ_NVQJ01000018.1.
DR AlphaFoldDB; P9WKE3; -.
DR SMR; P9WKE3; -.
DR STRING; 83332.Rv1017c; -.
DR PaxDb; P9WKE3; -.
DR DNASU; 885993; -.
DR GeneID; 45424988; -.
DR GeneID; 885993; -.
DR KEGG; mtu:Rv1017c; -.
DR TubercuList; Rv1017c; -.
DR eggNOG; COG0462; Bacteria.
DR OMA; FGWARQD; -.
DR PhylomeDB; P9WKE3; -.
DR UniPathway; UPA00087; UER00172.
DR UniPathway; UPA00963; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0002189; C:ribose phosphate diphosphokinase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0004749; F:ribose phosphate diphosphokinase activity; IDA:MTBBASE.
DR GO; GO:0006015; P:5-phosphoribose 1-diphosphate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IBA:GO_Central.
DR GO; GO:0009156; P:ribonucleoside monophosphate biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd06223; PRTases_typeI; 1.
DR Gene3D; 3.40.50.2020; -; 2.
DR HAMAP; MF_00583_B; RibP_PPkinase_B; 1.
DR InterPro; IPR000842; PRib_PP_synth_CS.
DR InterPro; IPR029099; Pribosyltran_N.
DR InterPro; IPR000836; PRibTrfase_dom.
DR InterPro; IPR029057; PRTase-like.
DR InterPro; IPR005946; Rib-P_diPkinase.
DR InterPro; IPR037515; Rib-P_diPkinase_bac.
DR PANTHER; PTHR10210; PTHR10210; 1.
DR Pfam; PF14572; Pribosyl_synth; 1.
DR Pfam; PF13793; Pribosyltran_N; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR01251; ribP_PPkin; 1.
DR PROSITE; PS00114; PRPP_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Cell wall biogenesis/degradation;
KW Cytoplasm; Isopeptide bond; Kinase; Magnesium; Manganese; Metal-binding;
KW Nucleotide biosynthesis; Nucleotide-binding; Reference proteome;
KW Transferase; Ubl conjugation.
FT CHAIN 1..326
FT /note="Ribose-phosphate pyrophosphokinase"
FT /id="PRO_0000141164"
FT ACT_SITE 202
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 45..47
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 104..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 138
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 178
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 204
FT /ligand="D-ribose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:78346"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 230
FT /ligand="D-ribose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:78346"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT BINDING 234..238
FT /ligand="D-ribose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:78346"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00583"
FT CROSSLNK 29
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-Cter in protein Pup)"
FT /evidence="ECO:0000269|PubMed:20066036"
SQ SEQUENCE 326 AA; 35477 MW; 4CE64D17E783AC37 CRC64;
MSHDWTDNRK NLMLFAGRAH PELAEQVAKE LDVHVTSQDA REFANGEIFV RFHESVRGCD
AFVLQSCPAP VNRWLMEQLI MIDALKRGSA KRITAVMPFY PYARQDKKHR GREPISARLI
ADLLKTAGAD RIVTVDLHTD QIQGFFDGPV DHMRGQNLLT GYIRDNYPDG NMVVVSPDSG
RVRIAEKWAD ALGGVPLAFI HKTRDPRVPN QVVSNRVVGD VAGRTCVLID DMIDTGGTIA
GAVALLHNDG AGDVIIAATH GVLSDPAAQR LASCGAREVI VTNTLPIGED KRFPQLTVLS
IAPLLASTIR AVFENGSVTG LFDGDA
