IPYR_MYCTU
ID IPYR_MYCTU Reviewed; 162 AA.
AC P9WI55; L0TG18; O06379; P65746;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Inorganic pyrophosphatase {ECO:0000303|PubMed:16239227};
DE EC=3.6.1.1 {ECO:0000269|PubMed:16239227, ECO:0000269|PubMed:26296329};
DE AltName: Full=Pyrophosphate phospho-hydrolase {ECO:0000255|HAMAP-Rule:MF_00209};
DE Short=PPase {ECO:0000303|PubMed:16239227};
GN Name=ppa {ECO:0000303|PubMed:11339880}; OrderedLocusNames=Rv3628;
GN ORFNames=MTCY15C10.24;
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 INDUCTION.
RX PubMed=11339880; DOI=10.1186/1471-2180-1-3;
RA Triccas J.A., Gicquel B.;
RT "Analysis of stress- and host cell-induced expression of the Mycobacterium
RT tuberculosis inorganic pyrophosphatase.";
RL BMC Microbiol. 1:3-3(2001).
RN [3]
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 [4]
RP FUNCTION, BIOTECHNOLOGY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=27097115; DOI=10.18632/oncotarget.8771;
RA Kim W.S., Kim J.S., Cha S.B., Kim H., Kwon K.W., Kim S.J., Han S.J.,
RA Choi S.Y., Cho S.N., Park J.H., Shin S.J.;
RT "Mycobacterium tuberculosis Rv3628 drives Th1-type T cell immunity via
RT TLR2-mediated activation of dendritic cells and displays vaccine potential
RT against the hyper-virulent Beijing K strain.";
RL Oncotarget 7:24962-24982(2016).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEX WITH SULFATE, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP MUTAGENESIS OF HIS-21 AND HIS-86.
RX PubMed=16239227; DOI=10.1074/jbc.m509489200;
RA Tammenkoski M., Benini S., Magretova N.N., Baykov A.A., Lahti R.;
RT "An unusual, His-dependent family I pyrophosphatase from Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 280:41819-41826(2005).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) IN COMPLEX WITH PHOSPHATE.
RX PubMed=21821883; DOI=10.1107/s1744309111023323;
RA Benini S., Wilson K.;
RT "Structure of the Mycobacterium tuberculosis soluble inorganic
RT pyrophosphatase Rv3628 at pH 7.0.";
RL Acta Crystallogr. F 67:866-870(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEXES WITH DIVALENT METAL
RP IONS; PYROPHOSPHATE AND PHOSPHATE IONS, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF ASP-54;
RP ASP-57 AND ASP-89, AND REACTION MECHANISM.
RX PubMed=26296329; DOI=10.1016/j.jsb.2015.08.010;
RA Pratt A.C., Dewage S.W., Pang A.H., Biswas T., Barnard-Britson S.,
RA Cisneros G.A., Tsodikov O.V.;
RT "Structural and computational dissection of the catalytic mechanism of the
RT inorganic pyrophosphatase from Mycobacterium tuberculosis.";
RL J. Struct. Biol. 192:76-87(2015).
CC -!- FUNCTION: Catalyzes the hydrolysis of inorganic pyrophosphate (PPi)
CC forming two phosphate ions. {ECO:0000269|PubMed:16239227,
CC ECO:0000269|PubMed:26296329}.
CC -!- FUNCTION: Antigen that activates dendritic cells (DCs), increasing
CC their expression of cell surface molecules and augmenting their
CC production of TNF-alpha, IL-1beta, IL-6, IL-23 and IL-12p70. Rv3628
CC mediates these effects by binding to TLR2 and activating downstream
CC MyD88-, MAPK- and NF-kappaB-dependent signaling pathways. Rv3628-
CC stimulated DCs induce the expansion of OVA-specific CD4+ and CD8+ T
CC cells which secrete IFN-gamma and IL-2, and the generation of
CC effector/memory T cells. Thus, Rv3628 polarizes DCs toward a Th1 immune
CC response and promotes protective immunity against M.tuberculosis
CC infection. Is not able to bind to TLR4 molecules on the cell surface.
CC {ECO:0000269|PubMed:27097115}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43474; EC=3.6.1.1; Evidence={ECO:0000269|PubMed:16239227,
CC ECO:0000269|PubMed:26296329};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16239227};
CC Note=Other metal ions such as Mn(2+) and Zn(2+) can support activity,
CC but at a much lower rate (PubMed:16239227). Three metal ions appear to
CC be required for the activation of the enzyme and the substrate during
CC the catalytic cycle (PubMed:26296329). {ECO:0000269|PubMed:16239227,
CC ECO:0000305|PubMed:26296329};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.3 uM for diphosphate (at pH 7.2) {ECO:0000269|PubMed:16239227};
CC KM=64 uM for diphosphate (at pH 7.5) {ECO:0000269|PubMed:26296329};
CC Note=kcat is 240 sec(-1) at pH 7.2 (PubMed:16239227). kcat is 48
CC sec(-1) at pH 7.5 (PubMed:26296329). {ECO:0000269|PubMed:16239227,
CC ECO:0000269|PubMed:26296329};
CC pH dependence:
CC Optimum pH is around 7.5. {ECO:0000269|PubMed:16239227};
CC -!- SUBUNIT: Homohexamer. {ECO:0000269|PubMed:16239227,
CC ECO:0000269|PubMed:26296329}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00209}.
CC Secreted {ECO:0000305|PubMed:27097115}. Host cell surface
CC {ECO:0000269|PubMed:27097115}.
CC -!- INDUCTION: Is constitutively expressed and is not up-regulated upon
CC macrophage infection or by exposure to environmental stress when grown
CC in vitro. {ECO:0000269|PubMed:11339880}.
CC -!- BIOTECHNOLOGY: Displays vaccine potential against the hyper-virulent
CC M.tuberculosis Beijing K strain. Protective efficacy is correlated with
CC the generation of Rv3628-specific CD4+ T cells co-producing IFN-gamma,
CC TNF-alpha and IL-2 and exhibiting an elevated IFN-gamma recall
CC response. {ECO:0000269|PubMed:27097115}.
CC -!- SIMILARITY: Belongs to the PPase family. {ECO:0000255|HAMAP-
CC Rule:MF_00209}.
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DR EMBL; AL123456; CCP46451.1; -; Genomic_DNA.
DR PIR; E70561; E70561.
DR RefSeq; NP_218145.1; NC_000962.3.
DR RefSeq; WP_003419577.1; NZ_NVQJ01000045.1.
DR PDB; 1SXV; X-ray; 1.30 A; A=1-162.
DR PDB; 1WCF; X-ray; 1.54 A; A=1-162.
DR PDB; 2UXS; X-ray; 2.70 A; A/B/C=2-162.
DR PDB; 4Z70; X-ray; 1.95 A; A/B/C=1-162.
DR PDB; 4Z71; X-ray; 1.85 A; A/B/C=1-162.
DR PDB; 4Z72; X-ray; 2.35 A; A=1-162.
DR PDB; 4Z73; X-ray; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-162.
DR PDB; 4Z74; X-ray; 2.55 A; A/B/C/D/E/F/G/H/I/J/K/L=1-162.
DR PDB; 5KDE; X-ray; 2.65 A; A=1-162.
DR PDB; 5KDF; X-ray; 2.45 A; A=1-162.
DR PDBsum; 1SXV; -.
DR PDBsum; 1WCF; -.
DR PDBsum; 2UXS; -.
DR PDBsum; 4Z70; -.
DR PDBsum; 4Z71; -.
DR PDBsum; 4Z72; -.
DR PDBsum; 4Z73; -.
DR PDBsum; 4Z74; -.
DR PDBsum; 5KDE; -.
DR PDBsum; 5KDF; -.
DR AlphaFoldDB; P9WI55; -.
DR SMR; P9WI55; -.
DR STRING; 83332.Rv3628; -.
DR BindingDB; P9WI55; -.
DR ChEMBL; CHEMBL3137292; -.
DR PaxDb; P9WI55; -.
DR DNASU; 885775; -.
DR GeneID; 885775; -.
DR KEGG; mtu:Rv3628; -.
DR TubercuList; Rv3628; -.
DR eggNOG; COG0221; Bacteria.
DR OMA; DEPTFPG; -.
DR PhylomeDB; P9WI55; -.
DR BRENDA; 3.6.1.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044228; C:host cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004427; F:inorganic diphosphatase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IDA:MTBBASE.
DR CDD; cd00412; pyrophosphatase; 1.
DR Gene3D; 3.90.80.10; -; 1.
DR HAMAP; MF_00209; Inorganic_PPase; 1.
DR InterPro; IPR008162; Pyrophosphatase.
DR InterPro; IPR036649; Pyrophosphatase_sf.
DR PANTHER; PTHR10286; PTHR10286; 1.
DR Pfam; PF00719; Pyrophosphatase; 1.
DR SUPFAM; SSF50324; SSF50324; 1.
DR PROSITE; PS00387; PPASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW Reference proteome; Secreted.
FT CHAIN 1..162
FT /note="Inorganic pyrophosphatase"
FT /id="PRO_0000137512"
FT ACT_SITE 89
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 16
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26296329"
FT BINDING 30
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26296329"
FT BINDING 42
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26296329"
FT BINDING 52
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 57
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 57
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:26296329"
FT BINDING 126
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26296329"
FT MUTAGEN 21
FT /note="H->K: 4-fold decrease in catalytic activity with
FT Mg(2+) as cofactor. 3-fold increase in catalytic activity
FT with Zn(2+) as cofactor. Shifts the pH for optimal activity
FT to 8.5."
FT /evidence="ECO:0000269|PubMed:16239227"
FT MUTAGEN 54
FT /note="D->N: 3-fold decrease in catalytic activity, and 2-
FT fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:26296329"
FT MUTAGEN 57
FT /note="D->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26296329"
FT MUTAGEN 86
FT /note="H->A: Nearly no effect on catalytic activity with
FT Mg(2+) as cofactor. 10-fold increase in catalytic activity
FT with Zn(2+) as cofactor."
FT /evidence="ECO:0000269|PubMed:16239227"
FT MUTAGEN 89
FT /note="D->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26296329"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:1SXV"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 71..84
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:1SXV"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1SXV"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:1SXV"
FT HELIX 113..125
FT /evidence="ECO:0007829|PDB:1SXV"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:1SXV"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:1SXV"
FT HELIX 143..158
FT /evidence="ECO:0007829|PDB:1SXV"
SQ SEQUENCE 162 AA; 18329 MW; 4ED0B35ECC7D1961 CRC64;
MQFDVTIEIP KGQRNKYEVD HETGRVRLDR YLYTPMAYPT DYGFIEDTLG DDGDPLDALV
LLPQPVFPGV LVAARPVGMF RMVDEHGGDD KVLCVPAGDP RWDHVQDIGD VPAFELDAIK
HFFVHYKDLE PGKFVKAADW VDRAEAEAEV QRSVERFKAG TH
