DB code: D00603

RLCP classification 9.5010.536180.109 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 Catalytic domain
E.C. 1.1.1.169
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 D00007 D00012 T00002 T00227
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A9J4 2-dehydropantoate 2-reductase
EC 1.1.1.169
Ketopantoate reductase
KPA reductase
KPR
NP_414959.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_488717.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
Q604L6
2-dehydropantoate 2-reductase
EC 1.1.1.169
YP_114934.1 (Protein)
NC_002977.6 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
B5RXG4
Ketopantoate reductase protein
EC 1.1.1.169
[Graphical View]
Q46RB9
Ketopantoate reductase ApbA/PanE
EC 1.1.1.169
YP_299159.1 (Protein)
NC_007348.1 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
Q39SB2
Ketopantoate reductase ApbA/PanE
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
O34661 Probable 2-dehydropantoate 2-reductase
EC 1.1.1.169
Ketopantoate reductase
KPA reductase
NP_389394.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
Q99R37
Similar to 2-dehydropantoate 2-reductase
NP_373124.1 (Protein)
NC_002758.2 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
Q831Q5
2-dehydropantoate 2-reductase, putative
NP_816093.1 (Protein)
NC_004668.1 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]
Q7MT04
2-dehydropantoate 2-reductase
NP_906247.1 (Protein)
NC_002950.2 (DNA/RNA sequence)
PF02558 (ApbA)
PF08546 (ApbA_C)
[Graphical View]

KEGG enzyme name
2-Dehydropantoate 2-reductase
2-Oxopantoate reductase
2-Ketopantoate reductase
2-Ketopantoic acid reductase
Ketopantoate reductase
Ketopantoic acid reductase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A9J4 PANE_ECOLI (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH. Monomer. Cytoplasm (Potential).
Q604L6 Q604L6_METCA (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
B5RXG4 B5RXG4_RALSO
Q46RB9 Q46RB9_CUPPJ (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
Q39SB2 Q39SB2_GEOMG (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
O34661 PANE_BACSU (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH. Cytoplasm (Potential).
Q99R37 Q99R37_STAAM (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
Q831Q5 Q831Q5_ENTFA (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.
Q7MT04 Q7MT04_PORGI (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH.

KEGG Pathways
Map code Pathways E.C.
MAP00770 Pantothenate and CoA biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00966 C00005 C00080 C00522 C00006
E.C.
Compound 2-dehydropantoate NADPH H+ (R)-pantoate NADP+
Type carbohydrate,carboxyl group amide group,amine group,nucleotide others carbohydrate,carboxyl group amide group,amine group,nucleotide
ChEBI 17094
 17094
 		16474
 16474
 		15378
 15378
 		18697
 18697
 		18009
 18009
PubChem 38
 38
 		5884
 5884
 		1038
 1038
 		439251
 439251
 		5886
 5886
1ks9A01 Unbound Unbound Unbound Unbound
1yjqA01 Unbound Unbound Unbound Bound:NAP
1yonA01 Unbound Unbound Unbound Analogue:APX
2ofpA01 Unbound Unbound Unbound Bound:NAP
2ofpB01 Unbound Unbound Unbound Bound:NAP
3i83A01 Unbound Unbound Unbound Unbound
3i83B01 Unbound Unbound Unbound Unbound
3ghyA01 Unbound Unbound Unbound Unbound
3ghyB01 Unbound Unbound Unbound Unbound
3hwrA01 Unbound Bound:NDP Unbound Unbound
3hwrB01 Unbound Bound:NDP Unbound Unbound
3hn2A01 Unbound Unbound Unbound Unbound
3hn2B01 Unbound Unbound Unbound Unbound
3hn2C01 Unbound Unbound Unbound Unbound
3hn2D01 Unbound Unbound Unbound Unbound
3egoA01 Unbound Unbound Unbound Unbound
3egoB01 Unbound Unbound Unbound Unbound
3g17A01 Unbound Unbound Unbound Unbound
3g17B01 Unbound Unbound Unbound Unbound
3g17C01 Unbound Unbound Unbound Unbound
3g17D01 Unbound Unbound Unbound Unbound
3g17E01 Unbound Unbound Unbound Unbound
3g17F01 Unbound Unbound Unbound Unbound
3g17G01 Unbound Unbound Unbound Unbound
3g17H01 Unbound Unbound Unbound Unbound
2ew2A01 Unbound Unbound Unbound Unbound
2ew2B01 Unbound Unbound Unbound Unbound
2qytA01 Unbound Unbound Unbound Unbound
1ks9A02 Unbound Unbound Unbound Unbound
1yjqA02 Unbound Unbound Unbound Unbound
1yonA02 Unbound Unbound Unbound Unbound
2ofpA02 Unbound Unbound Bound:PAF Unbound
2ofpB02 Unbound Unbound Bound:PAF Unbound
3i83A02 Unbound Unbound Unbound Unbound
3i83B02 Unbound Unbound Unbound Unbound
3ghyA02 Unbound Unbound Unbound Unbound
3ghyB02 Unbound Unbound Unbound Unbound
3hwrA02 Unbound Unbound Unbound Unbound
3hwrB02 Unbound Unbound Unbound Unbound
3hn2A02 Unbound Unbound Unbound Unbound
3hn2B02 Unbound Unbound Unbound Unbound
3hn2C02 Unbound Unbound Unbound Unbound
3hn2D02 Unbound Unbound Unbound Unbound
3egoA02 Unbound Unbound Unbound Unbound
3egoB02 Unbound Unbound Unbound Unbound
3g17A02 Unbound Unbound Unbound Unbound
3g17B02 Unbound Unbound Unbound Unbound
3g17C02 Unbound Unbound Unbound Unbound
3g17D02 Unbound Unbound Unbound Unbound
3g17E02 Unbound Unbound Unbound Unbound
3g17F02 Unbound Unbound Unbound Unbound
3g17G02 Unbound Unbound Unbound Unbound
3g17H02 Unbound Unbound Unbound Unbound
2ew2A02 Unbound Unbound Unbound Unbound
2ew2B02 Unbound Unbound Unbound Unbound
2qytA02 Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1], [2], [3], [4], [6] & Swiss;O34661, P0A9J4 & CSA;1yon

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ks9A01 ASN 98 ASN 98
1yjqA01 ASN 98 ASN 98
1yonA01 ASN 98 ASN 98
2ofpA01 ASN 98 ASN 98
2ofpB01 ASN 98 ASN 98
3i83A01 ASN 104 ASN 104
3i83B01 ASN 104 ASN 104 invisible 62-70, 77-83, 95-97, 118-119
3ghyA01 ASN 103 ASN 103
3ghyB01 ASN 103 ASN 103
3hwrA01 ASN 102 ASN 102
3hwrB01 ASN 102 ASN 102
3hn2A01 ASN 102 ASN 102
3hn2B01 ASN 102 ASN 102
3hn2C01 ASN 102 ASN 102
3hn2D01 ASN 102 ASN 102
3egoA01 ASN 98 ASN 98
3egoB01 ASN 98 ASN 98
3g17A01 ASN 97 ASN 97
3g17B01 ASN 97 ASN 97
3g17C01 ASN 97 ASN 97
3g17D01 ASN 97 ASN 97
3g17E01 ASN 97 ASN 97
3g17F01 ASN 97 ASN 97
3g17G01 ASN 97 ASN 97
3g17H01 ASN 97 ASN 97
2ew2A01 ASN 106 ASN 106
2ew2B01 ASN 106 ASN 106
2qytA01 ASN 115 ASN 115
1ks9A02 LYS 176;GLU 256
1yjqA02 LYS 176;GLU 256
1yonA02 LYS 176;GLU 256
2ofpA02 LYS 176;GLU 256
2ofpB02 LYS 176;GLU 256
3i83A02 LYS 186;GLU 267
3i83B02 LYS 186;GLU 267
3ghyA02 LYS 204;GLU 286 invisible 277-281
3ghyB02 LYS 204;GLU 286 invisible 269-271
3hwrA02 LYS 178;GLU 260
3hwrB02 LYS 178;GLU 260
3hn2A02 LYS 184;GLU 268
3hn2B02 LYS 184;GLU 268
3hn2C02 LYS 184;GLU 268
3hn2D02 LYS 184;GLU 268
3egoA02 LYS 179;GLU 258
3egoB02 LYS 179;GLU 258
3g17A02 LYS 169;GLU 251
3g17B02 LYS 169;GLU 251
3g17C02 LYS 169;GLU 251
3g17D02 LYS 169;GLU 251
3g17E02 LYS 169;GLU 251
3g17F02 LYS 169;GLU 251
3g17G02 LYS 169;GLU 251
3g17H02 LYS 169;GLU 251
2ew2A02 LYS 188;GLU 274
2ew2B02 LYS 188;GLU 274
2qytA02 LYS 198; inivisible 261-280

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 11123955
Journal Biochemistry
Year 2000
Volume 39
Pages 16244-51
Authors Zheng R, Blanchard JS
Title Identification of active site residues in E. coli ketopantoate reductase by mutagenesis and chemical rescue.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), PROTEIN SEQUENCE OF 1-9, MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
Medline ID
PubMed ID 11724562
Journal Biochemistry
Year 2001
Volume 40
Pages 14493-500
Authors Matak-Vinkovi? D, Vinkovi? M, Saldanha SA, Ashurst JL, von Delft F, Inoue T, Miguel RN, Smith AG, Blundell TL, Abell C
Title Crystal structure of Escherichia coli ketopantoate reductase at 1.7 A resolution and insight into the enzyme mechanism.
Related PDB 1ks9
Related UniProtKB P0A9J4
[3]
Resource
Comments
Medline ID
PubMed ID 15565250
Journal Nat Prod Rep
Year 2004
Volume 21
Pages 695-721
Authors Webb ME, Smith AG, Abell C
Title Biosynthesis of pantothenate.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) IN COMPLEX WITH NADP.
Medline ID
PubMed ID 15966718
Journal Biochemistry
Year 2005
Volume 44
Pages 8930-9
Authors Lobley CM, Ciulli A, Whitney HM, Williams G, Smith AG, Abell C, Blundell TL
Title The crystal structure of Escherichia coli ketopantoate reductase with NADP+ bound.
Related PDB 1yjq
Related UniProtKB P0A9J4
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH NADP ANALOG, MUTAGENESIS OF ASN-98; LYS-176 AND GLU-256.
Medline ID
PubMed ID 17242510
Journal Acta Crystallogr D Biol Crystallogr
Year 2007
Volume 63
Pages 171-8
Authors Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C
Title pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study.
Related PDB 1yon
Related UniProtKB P0A9J4
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND NADP, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-72 AND SER-244.
Medline ID
PubMed ID 17229734
Journal J Biol Chem
Year 2007
Volume 282
Pages 8487-97
Authors Ciulli A, Chirgadze DY, Smith AG, Blundell TL, Abell C
Title Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity.
Related PDB 2ofp
Related UniProtKB P0A9J4

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.

Created Updated
2010-03-23 2012-02-24