EzCatDB: D00603
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DB codeD00603
RLCP classification9.5010.536180.109 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
Domain 21.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2Catalytic domain
E.C.1.1.1.169

CATH domainRelated DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2D00007,D00012,T00002,T00227
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109

Enzyme Name
UniProtKBKEGG

P0A9J4Q604L6B5RXG4Q46RB9Q39SB2O34661Q99R37Q831Q5Q7MT04
Protein name2-dehydropantoate 2-reductase



Probable 2-dehydropantoate 2-reductase


2-Dehydropantoate 2-reductase
2-Oxopantoate reductase
2-Ketopantoate reductase
2-Ketopantoic acid reductase
Ketopantoate reductase
Ketopantoic acid reductase
SynonymsEC 1.1.1.169
Ketopantoate reductase
KPA reductase
KPR
2-dehydropantoate 2-reductase
EC 1.1.1.169
Ketopantoate reductase protein
EC 1.1.1.169
Ketopantoate reductase ApbA/PanE
EC 1.1.1.169
Ketopantoate reductase ApbA/PanE
EC 1.1.1.169
Ketopantoate reductase
KPA reductase
Similar to 2-dehydropantoate 2-reductase
2-dehydropantoate 2-reductase, putative
2-dehydropantoate 2-reductase
RefSeqNP_414959.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_488717.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
YP_114934.1 (Protein)
NC_002977.6 (DNA/RNA sequence)
YP_299159.1 (Protein)
NC_007348.1 (DNA/RNA sequence)

NP_389394.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
NP_373124.1 (Protein)
NC_002758.2 (DNA/RNA sequence)
NP_816093.1 (Protein)
NC_004668.1 (DNA/RNA sequence)
NP_906247.1 (Protein)
NC_002950.2 (DNA/RNA sequence)
PfamPF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00770Pantothenate and CoA biosynthesis

UniProtKB:Accession NumberP0A9J4Q604L6B5RXG4Q46RB9Q39SB2O34661Q99R37Q831Q5Q7MT04
Entry namePANE_ECOLIQ604L6_METCAB5RXG4_RALSOQ46RB9_CUPPJQ39SB2_GEOMGPANE_BACSUQ99R37_STAAMQ831Q5_ENTFAQ7MT04_PORGI
Activity(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
SubunitMonomer.







Subcellular locationCytoplasm (Potential).



Cytoplasm (Potential).


Cofactor









Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00966C00005C00080C00522C00006
Compound2-dehydropantoateNADPHH+(R)-pantoateNADP+
Typecarbohydrate,carboxyl groupamide group,amine group,nucleotideotherscarbohydrate,carboxyl groupamide group,amine group,nucleotide
ChEBI17094
16474
15378
18697
18009
PubChem38
5884
1038
439251
5886
             
1ks9A01UnboundUnbound UnboundUnbound
1yjqA01UnboundUnbound UnboundBound:NAP
1yonA01UnboundUnbound UnboundAnalogue:APX
2ofpA01UnboundUnbound UnboundBound:NAP
2ofpB01UnboundUnbound UnboundBound:NAP
3i83A01UnboundUnbound UnboundUnbound
3i83B01UnboundUnbound UnboundUnbound
3ghyA01UnboundUnbound UnboundUnbound
3ghyB01UnboundUnbound UnboundUnbound
3hwrA01UnboundBound:NDP UnboundUnbound
3hwrB01UnboundBound:NDP UnboundUnbound
3hn2A01UnboundUnbound UnboundUnbound
3hn2B01UnboundUnbound UnboundUnbound
3hn2C01UnboundUnbound UnboundUnbound
3hn2D01UnboundUnbound UnboundUnbound
3egoA01UnboundUnbound UnboundUnbound
3egoB01UnboundUnbound UnboundUnbound
3g17A01UnboundUnbound UnboundUnbound
3g17B01UnboundUnbound UnboundUnbound
3g17C01UnboundUnbound UnboundUnbound
3g17D01UnboundUnbound UnboundUnbound
3g17E01UnboundUnbound UnboundUnbound
3g17F01UnboundUnbound UnboundUnbound
3g17G01UnboundUnbound UnboundUnbound
3g17H01UnboundUnbound UnboundUnbound
2ew2A01UnboundUnbound UnboundUnbound
2ew2B01UnboundUnbound UnboundUnbound
2qytA01UnboundUnbound UnboundUnbound
1ks9A02UnboundUnbound UnboundUnbound
1yjqA02UnboundUnbound UnboundUnbound
1yonA02UnboundUnbound UnboundUnbound
2ofpA02UnboundUnbound Bound:PAFUnbound
2ofpB02UnboundUnbound Bound:PAFUnbound
3i83A02UnboundUnbound UnboundUnbound
3i83B02UnboundUnbound UnboundUnbound
3ghyA02UnboundUnbound UnboundUnbound
3ghyB02UnboundUnbound UnboundUnbound
3hwrA02UnboundUnbound UnboundUnbound
3hwrB02UnboundUnbound UnboundUnbound
3hn2A02UnboundUnbound UnboundUnbound
3hn2B02UnboundUnbound UnboundUnbound
3hn2C02UnboundUnbound UnboundUnbound
3hn2D02UnboundUnbound UnboundUnbound
3egoA02UnboundUnbound UnboundUnbound
3egoB02UnboundUnbound UnboundUnbound
3g17A02UnboundUnbound UnboundUnbound
3g17B02UnboundUnbound UnboundUnbound
3g17C02UnboundUnbound UnboundUnbound
3g17D02UnboundUnbound UnboundUnbound
3g17E02UnboundUnbound UnboundUnbound
3g17F02UnboundUnbound UnboundUnbound
3g17G02UnboundUnbound UnboundUnbound
3g17H02UnboundUnbound UnboundUnbound
2ew2A02UnboundUnbound UnboundUnbound
2ew2B02UnboundUnbound UnboundUnbound
2qytA02UnboundUnbound UnboundUnbound

Active-site residues
resource
literature [1], [2], [3], [4], [6] & Swiss;O34661, P0A9J4 & CSA;1yon
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1ks9A01ASN  98
ASN  98
 
1yjqA01ASN  98
ASN  98
 
1yonA01ASN  98
ASN  98
 
2ofpA01ASN  98
ASN  98
 
2ofpB01ASN  98
ASN  98
 
3i83A01ASN 104
ASN 104
 
3i83B01ASN 104
ASN 104
invisible 62-70, 77-83, 95-97, 118-119
3ghyA01ASN 103
ASN 103
 
3ghyB01ASN 103
ASN 103
 
3hwrA01ASN 102
ASN 102
 
3hwrB01ASN 102
ASN 102
 
3hn2A01ASN 102
ASN 102
 
3hn2B01ASN 102
ASN 102
 
3hn2C01ASN 102
ASN 102
 
3hn2D01ASN 102
ASN 102
 
3egoA01ASN  98
ASN  98
 
3egoB01ASN  98
ASN  98
 
3g17A01ASN  97
ASN  97
 
3g17B01ASN  97
ASN  97
 
3g17C01ASN  97
ASN  97
 
3g17D01ASN  97
ASN  97
 
3g17E01ASN  97
ASN  97
 
3g17F01ASN  97
ASN  97
 
3g17G01ASN  97
ASN  97
 
3g17H01ASN  97
ASN  97
 
2ew2A01ASN 106
ASN 106
 
2ew2B01ASN 106
ASN 106
 
2qytA01ASN 115
ASN 115
 
1ks9A02LYS 176;GLU 256
 
 
1yjqA02LYS 176;GLU 256
 
 
1yonA02LYS 176;GLU 256
 
 
2ofpA02LYS 176;GLU 256
 
 
2ofpB02LYS 176;GLU 256
 
 
3i83A02LYS 186;GLU 267
 
 
3i83B02LYS 186;GLU 267
 
 
3ghyA02LYS 204;GLU 286
 
invisible 277-281
3ghyB02LYS 204;GLU 286
 
invisible 269-271
3hwrA02LYS 178;GLU 260
 
 
3hwrB02LYS 178;GLU 260
 
 
3hn2A02LYS 184;GLU 268
 
 
3hn2B02LYS 184;GLU 268
 
 
3hn2C02LYS 184;GLU 268
 
 
3hn2D02LYS 184;GLU 268
 
 
3egoA02LYS 179;GLU 258
 
 
3egoB02LYS 179;GLU 258
 
 
3g17A02LYS 169;GLU 251
 
 
3g17B02LYS 169;GLU 251
 
 
3g17C02LYS 169;GLU 251
 
 
3g17D02LYS 169;GLU 251
 
 
3g17E02LYS 169;GLU 251
 
 
3g17F02LYS 169;GLU 251
 
 
3g17G02LYS 169;GLU 251
 
 
3g17H02LYS 169;GLU 251
 
 
2ew2A02LYS 188;GLU 274
 
 
2ew2B02LYS 188;GLU 274
 
 
2qytA02LYS 198;       
 
inivisible 261-280

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme 2, p.16248-16251
[2]p.14499
[3]Scheme 9, p.704-708
[4]Fig.7, p.8935-3937
[6]Scheme 2, p.8495-8496

references
[1]
PubMed ID11123955
JournalBiochemistry
Year2000
Volume39
Pages16244-51
AuthorsZheng R, Blanchard JS
TitleIdentification of active site residues in E. coli ketopantoate reductase by mutagenesis and chemical rescue.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), PROTEIN SEQUENCE OF 1-9, MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
PubMed ID11724562
JournalBiochemistry
Year2001
Volume40
Pages14493-500
AuthorsMatak-Vinkovi? D, Vinkovi? M, Saldanha SA, Ashurst JL, von Delft F, Inoue T, Miguel RN, Smith AG, Blundell TL, Abell C
TitleCrystal structure of Escherichia coli ketopantoate reductase at 1.7 A resolution and insight into the enzyme mechanism.
Related PDB1ks9
Related UniProtKBP0A9J4
[3]
PubMed ID15565250
JournalNat Prod Rep
Year2004
Volume21
Pages695-721
AuthorsWebb ME, Smith AG, Abell C
TitleBiosynthesis of pantothenate.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) IN COMPLEX WITH NADP.
PubMed ID15966718
JournalBiochemistry
Year2005
Volume44
Pages8930-9
AuthorsLobley CM, Ciulli A, Whitney HM, Williams G, Smith AG, Abell C, Blundell TL
TitleThe crystal structure of Escherichia coli ketopantoate reductase with NADP+ bound.
Related PDB1yjq
Related UniProtKBP0A9J4
[5]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH NADP ANALOG, MUTAGENESIS OF ASN-98; LYS-176 AND GLU-256.
PubMed ID17242510
JournalActa Crystallogr D Biol Crystallogr
Year2007
Volume63
Pages171-8
AuthorsCiulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C
TitlepH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study.
Related PDB1yon
Related UniProtKBP0A9J4
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND NADP, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-72 AND SER-244.
PubMed ID17229734
JournalJ Biol Chem
Year2007
Volume282
Pages8487-97
AuthorsCiulli A, Chirgadze DY, Smith AG, Blundell TL, Abell C
TitleCrystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity.
Related PDB2ofp
Related UniProtKBP0A9J4

comments
According to the literature [6], this enzyme catalyzes the following reaction:
(0) The sidechain of Glu256 and the amide groups of both sidechain and mainchain of Asn98 may modulate the activity of nicotinamide group through ribose hydroxyl groups. Moreover, the sidechain of Asn98 might modulate the activity of Lys176 as well as the substrate through its carboxyl group.
(1) The pro-S hydride of NADPH transfers to the si-face of substrate, 2-dehydropantoate (or ketopantoate). At the same time, Lys176 acts as a general acid to protonate the C2 carbonyl oxygen during the developing C2-alkoxide.

createdupdated
2010-03-232012-02-24


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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