DB code: S00602

RLCP classification 9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.10
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 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 D00603 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
Q7Z4W1 L-xylulose reductase
XR
EC 1.1.1.10
Dicarbonyl/L-xylulose reductase
Kidney dicarbonyl reductase
kiDCR
Carbonyl reductase II
Sperm surface protein P34H
NP_001182147.1 (Protein)
NM_001195218.1 (DNA/RNA sequence)
NP_057370.1 (Protein)
NM_016286.3 (DNA/RNA sequence)

KEGG enzyme name
L-Xylulose reductase
Xylitol dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q7Z4W1 DCXR_HUMAN Xylitol + NADP(+) = L-xylulose + NADPH. Homotetramer. Membrane, peripheral membrane protein (By similarity). Probably recruited to membranes via an interaction with phosphatidylinositol (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00040 Pentose and glucuronate interconversions

Compound table
Substrates Products Intermediates
KEGG-id C00312 C00005 C00080 C00379 C00006
E.C.
Compound L-xylulose NADPH H+ xylitol NADP+
Type carbohydrate amide group,amine group,nucleotide others carbohydrate amide group,amine group,nucleotide
ChEBI 16474
 16474
 		15378
 15378
 		17151
 17151
 		18009
 18009
PubChem 439205
 439205
 		5884
 5884
 		1038
 1038
 		5886
 5886
1pr9A00 Unbound Unbound Unbound Bound:NAP
1pr9B00 Unbound Unbound Unbound Bound:NAP
1wntA00 Unbound Unbound Unbound Bound:NAP
1wntB00 Unbound Unbound Unbound Bound:NAP
1wntC00 Unbound Unbound Unbound Bound:NAP
1wntD00 Unbound Unbound Unbound Bound:NAP
3d3wA00 Unbound Unbound Unbound Bound:NAP
3d3wB00 Unbound Unbound Unbound Bound:NAP

Reference for Active-site residues
resource references E.C.
literature;[4], [6], [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1pr9A00 SER 136;TYR 149;LYS 153
1pr9B00 SER 136;TYR 149;LYS 153
1wntA00 SER 136;TYR 149;LYS 153
1wntB00 SER 136;TYR 149;LYS 153
1wntC00 SER 136;TYR 149;LYS 153
1wntD00 SER 136;TYR 149;LYS 153
3d3wA00 SER 136;TYR 149;LYS 153
3d3wB00 SER 136;TYR 149;LYS 153

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.545-6, Table.1
[6]
p.729-31
[7]
p.431, Fig.7

References
[1]
Resource
Comments
Medline ID
PubMed ID 8805511
Journal Structure
Year 1996
Volume 4
Pages 33-45
Authors Tanaka N, Nonaka T, Nakanishi M, Deyashiki Y, Hara A, Mitsui Y
Title Crystal structure of the ternary complex of mouse lung carbonyl reductase at 1.8 A resolution: the structural origin of coenzyme specificity in the short-chain dehydrogenase/reductase family.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS).
Medline ID
PubMed ID 12136162
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 1379-80
Authors El-Kabbani O, Chung RP, Ishikura S, Usami N, Nakagawa J, Hara A
Title Crystallization and preliminary crystallographic analysis of human L-xylulose reductase.
Related PDB
Related UniProtKB Q7Z4W1
[3]
Resource
Comments
Medline ID
PubMed ID 11882650
Journal J Biol Chem
Year 2002
Volume 277
Pages 17883-91
Authors Nakagawa J, Ishikura S, Asami J, Isaji T, Usami N, Hara A, Sakurai T, Tsuritani K, Oda K, Takahashi M, Yoshimoto M, Otsuka N, Kitamura K
Title Molecular characterization of mammalian dicarbonyl/L-xylulose reductase and its localization in kidney.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12604240
Journal Chem Biol Interact
Year 2003
Volume 143-144
Pages 543-50
Authors Ishikura S, Isaji T, Usami N, Nakagawa J, El-Kabbani O, Hara A
Title Identification of amino acid residues involved in substrate recognition of L-xylulose reductase by site-directed mutagenesis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12604210
Journal Chem Biol Interact
Year 2003
Volume 143-144
Pages 247-53
Authors Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H
Title Short-chain dehydrogenases/reductases (SDR): the 2002 update.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH NADP AND SUBSTRATE, AND MUTAGENESIS OF ASN-107.
Medline ID
PubMed ID 15103634
Journal Proteins
Year 2004
Volume 55
Pages 724-32
Authors El-Kabbani O, Ishikura S, Darmanin C, Carbone V, Chung RP, Usami N, Hara A
Title Crystal structure of human L-xylulose reductase holoenzyme: probing the role of Asn107 with site-directed mutagenesis.
Related PDB 1pr9
Related UniProtKB Q7Z4W1
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY
Medline ID
PubMed ID 15906319
Journal Proteins
Year 2005
Volume 60
Pages 424-32
Authors El-Kabbani O, Carbone V, Darmanin C, Ishikura S, Hara A
Title Structure of the tetrameric form of human L-Xylulose reductase: probing the inhibitor-binding site with molecular modeling and site-directed mutagenesis.
Related PDB 1wnt
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 19337691
Journal Cell Mol Life Sci
Year 2009
Volume 66
Pages 1570-9
Authors Zhao HT, Endo S, Ishikura S, Chung R, Hogg PJ, Hara A, El-Kabbani O
Title Structure/function analysis of a critical disulfide bond in the active site of L-xylulose reductase.
Related PDB 3d3w
Related UniProtKB

Comments
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. The conformation of these residues, compared to that of the NAD molecule, seems to be similar to that of the homologous enzymes. Thus, this enzyme catalyzes hydride transfer reaction from NADH to substrate.
Moreover, there is a disulfide bond between Cys138 and Cys150, whose conformation seems to be structurally unstable, near the active site (see [8]). This property is very unique to this enzyme, compared to the other homologous enzymes. The disulfide bond might be involved in regulation of the enzyme activity, through its S-cysteinylation (see [8]).

Created Updated
2008-11-05 2011-07-19