PANE_MYCTU
ID PANE_MYCTU Reviewed; 295 AA.
AC P9WIL1; L0TBN6; Q50648;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=2-dehydropantoate 2-reductase {ECO:0000250|UniProtKB:P0A9J4};
DE EC=1.1.1.169 {ECO:0000250|UniProtKB:P0A9J4};
DE AltName: Full=Ketopantoate reductase {ECO:0000250|UniProtKB:P0A9J4};
DE Short=KPR {ECO:0000250|UniProtKB:P0A9J4};
GN OrderedLocusNames=Rv2573; ORFNames=MTCY227.28c;
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 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 [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] {ECO:0007744|PDB:4OL9}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 2-295 IN COMPLEX WITH NADP.
RG Seattle Structural Genomics Center for Infectious Disease (SSGCID);
RA Dranow D.M., Wernimont A.K., Abendroth A., Pierce P.G., Bullen J.,
RA Edwards T.E., Lorimer D.;
RT "Crystal structure of putative 2-dehydropantoate 2-reductase PanE from
RT Mycobacterium tuberculosis complexed with NADP and oxamate.";
RL Submitted (JAN-2014) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of ketopantoate into
CC pantoic acid. {ECO:0000250|UniProtKB:P0A9J4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-pantoate + NADP(+) = 2-dehydropantoate + H(+) + NADPH;
CC Xref=Rhea:RHEA:16233, ChEBI:CHEBI:11561, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15980, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.169; Evidence={ECO:0000250|UniProtKB:P0A9J4};
CC -!- PATHWAY: Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)-
CC pantoate from 3-methyl-2-oxobutanoate: step 2/2.
CC {ECO:0000250|UniProtKB:P0A9J4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P0A9J4}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the ketopantoate reductase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP45369.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP45369.1; ALT_INIT; Genomic_DNA.
DR PIR; D70724; D70724.
DR RefSeq; NP_217089.3; NC_000962.3.
DR PDB; 4OL9; X-ray; 1.85 A; A=2-295.
DR PDBsum; 4OL9; -.
DR AlphaFoldDB; P9WIL1; -.
DR SMR; P9WIL1; -.
DR STRING; 83332.Rv2573; -.
DR PaxDb; P9WIL1; -.
DR DNASU; 888188; -.
DR GeneID; 888188; -.
DR KEGG; mtu:Rv2573; -.
DR PATRIC; fig|83332.12.peg.2881; -.
DR TubercuList; Rv2573; -.
DR eggNOG; COG1893; Bacteria.
DR OMA; GMFSRGD; -.
DR UniPathway; UPA00028; UER00004.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0008677; F:2-dehydropantoate 2-reductase activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR GO; GO:0015940; P:pantothenate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR003710; ApbA.
DR InterPro; IPR013752; KPA_reductase.
DR InterPro; IPR013332; KPR_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02558; ApbA; 1.
DR Pfam; PF08546; ApbA_C; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00745; apbA_panE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; NADP; Oxidoreductase; Pantothenate biosynthesis;
KW Reference proteome.
FT CHAIN 1..295
FT /note="2-dehydropantoate 2-reductase"
FT /id="PRO_0000157316"
FT ACT_SITE 177
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 10..13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 33..34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 74
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 84
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 100
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 126
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 255..258
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:4OL9"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 12..24
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 78..88
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 115..123
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 148..159
FT /evidence="ECO:0007829|PDB:4OL9"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 170..190
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 194..198
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 200..219
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 228..238
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 246..252
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 264..270
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:4OL9"
FT HELIX 278..292
FT /evidence="ECO:0007829|PDB:4OL9"
SQ SEQUENCE 295 AA; 31033 MW; BB2782E105F536C8 CRC64;
MATGIALVGP GAVGTTVAAL LHKAGYSPLL CGHTPRAGIE LRRDGADPIV VPGPVHTSPR
EVAGPVDVLI LAVKATQNDA ARPWLTRLCD ERTVVAVLQN GVEQVEQVQP HCPSSAVVPA
IVWCSAETQP QGWVRLRGEA ALVVPTGPAA EQFAGLLRGA GATVDCDPDF TTAAWRKLLV
NALAGFMVLS GRRSAMFRRD DVAALSRRYV AECLAVARAE GARLDDDVVD EVVRLVRSAP
QDMGTSMLAD RAAHRPLEWD LRNGVIVRKA RAHGLATPIS DVLVPLLAAA SDGPG
