O74237 (XYL1_CANTE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD(P)H-dependent D-xylose reductase
Short name=XR
EC=1.1.1.-

Gene names

Name:	XYL1
Synonyms:	XYLR

Organism

Candida tenuis (Yeast)

Taxonomic identifier

45596 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › mitosporic Saccharomycetales › Candida

Protein attributes

Sequence length	322 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reduces D-xylose into xylitol. Has a preference for NADPH, but can also utilize NADH as cosubstrate.
Pathway	Carbohydrate metabolism; D-xylose degradation.
Subunit structure	Homodimer. Ref.2 Ref.3
Sequence similarities	Belongs to the aldo/keto reductase family.
Biophysicochemical properties	Kinetic parameters: KM=142 mM for xylose Ref.4 Ref.6 KM=38 µM for NADH KM=3 µM for NADPH

Ontologies

Keywords
Biological process	Carbohydrate metabolism Xylose metabolism
Ligand	NAD NADP
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	D-xylose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 322

322

NAD(P)H-dependent D-xylose reductase

PRO_0000124661

Regions

Nucleotide binding

169 – 170

2

NAD or NADP

Nucleotide binding

218 – 227

10

NAD or NADP

Nucleotide binding

274 – 284

11

NAD or NADP

Sites

Active site

52

1

Proton donor

Binding site

114

1

Substrate By similarity

Site

81

1

Lowers pKa of active site Tyr By similarity

Experimental info

Mutagenesis

24

1

W → F or Y: Strongly reduced affinity for xylose. Reduces NADH-dependent enzyme activity by over 96%. Ref.6

Mutagenesis

51

1

D → A: Slightly reduced enzyme activity. Ref.6

Mutagenesis

274

1

K → E: Reduces enzyme activity about 1000-fold. Ref.4

Mutagenesis

274

1

K → G or M: Reduces affinity for NAD and NADP. Ref.4

Mutagenesis

274

1

K → R: Increases affinity for NAD. Strongly reduced enzyme activity with NADP; when associated with D-276. Ref.4

Mutagenesis

275

1

S → A: Decreases affinity for NAD and NADP. Ref.4

Mutagenesis

276

1

N → D: Increases affinitiy for NAD. Decreases affinity for NADP. Strongly reduced enzyme activity with NADP; when associated with R-274. Ref.4

Mutagenesis

280

1

R → H: Increases affinity for NAD. Ref.4

Mutagenesis

310

1

N → A or D: Strongly decreased affinity for xylose. Ref.6

Secondary structure

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322

Helix Strand Turn

Details...

Beta strand

7 – 9

3

Beta strand

15 – 22

8

Helix

28 – 40

13

Beta strand

45 – 47

3

Helix

50 – 52

3

Helix

55 – 67

13

Helix

73 – 75

3

Beta strand

77 – 82

6

Helix

84 – 86

3

Helix

89 – 103

15

Beta strand

108 – 113

6

Turn

124 – 126

3

Helix

147 – 159

13

Beta strand

162 – 170

9

Helix

173 – 182

10

Beta strand

189 – 193

5

Helix

201 – 209

9

Beta strand

213 – 217

5

Turn

239 – 241

3

Helix

243 – 252

10

Helix

256 – 265

10

Turn

266 – 268

3

Helix

280 – 283

4

Helix

294 – 301

8

Helix

313 – 316

4

Sequences

	Sequence		Length	Mass (Da)
	O74237 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 4C74A8FBC9357690	FASTA	322	36,021
	10 20 30 40 50 60 MSASIPDIKL SSGHLMPSIG FGCWKLANAT AGEQVYQAIK AGYRLFDGAE DYGNEKEVGD 70 80 90 100 110 120 GVKRAIDEGL VKREEIFLTS KLWNNYHDPK NVETALNKTL ADLKVDYVDL FLIHFPIAFK 130 140 150 160 170 180 FVPIEEKYPP GFYCGDGNNF VYEDVPILET WKALEKLVAA GKIKSIGVSN FPGALLLDLL 190 200 210 220 230 240 RGATIKPAVL QVEHHPYLQQ PKLIEFAQKA GVTITAYSSF GPQSFVEMNQ GRALNTPTLF 250 260 270 280 290 300 AHDTIKAIAA KYNKTPAEVL LRWAAQRGIA VIPKSNLPER LVQNRSFNTF DLTKEDFEEI 310 320 AKLDIGLRFN DPWDWDNIPI FV

References

[1]	"Xylose utilisation: cloning and characterisation of the xylose reductase from Candida tenuis." Hacker B., Habenicht A., Kiess M., Mattes R. Biol. Chem. 380:1395-1403(1999) [PubMed: 10661866] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CBS 4435.
[2]	"The structure of apo and holo forms of xylose reductase, a dimeric aldo-keto reductase from Candida tenuis." Kavanagh K.L., Klimacek M., Nidetzky B., Wilson D.K. Biochemistry 41:8785-8795(2002) [PubMed: 12102621] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBUNIT.
[3]	"Structure of xylose reductase bound to NAD+ and the basis for single and dual co-substrate specificity in family 2 aldo-keto reductases." Kavanagh K.L., Klimacek M., Nidetzky B., Wilson D.K. Biochem. J. 373:319-326(2003) [PubMed: 12733986] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NAD, SUBUNIT.
[4]	"The coenzyme specificity of Candida tenuis xylose reductase (AKR2B5) explored by site-directed mutagenesis and X-ray crystallography." Petschacher B., Leitgeb S., Kavanagh K.L., Wilson D.K., Nidetzky B. Biochem. J. 385:75-83(2005) [PubMed: 15320875] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ARG-274/ASP-276 IN COMPLEX WITH NAD, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-274; SER-275; ASN-276 AND ARG-280.
[5]	"Fine tuning of coenzyme specificity in family 2 aldo-keto reductases revealed by crystal structures of the Lys-274-->Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD+ and NADP+." Leitgeb S., Petschacher B., Wilson D.K., Nidetzky B. FEBS Lett. 579:763-767(2005) [PubMed: 15670843] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-274 IN COMPLEXES WITH NAD AND NADP.
[6]	"Probing the substrate binding site of Candida tenuis xylose reductase (AKR2B5) with site-directed mutagenesis." Kratzer R., Leitgeb S., Wilson D.K., Nidetzky B. Biochem. J. 393:51-58(2006) [PubMed: 16336198] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2-322 OF MUTANT ASP-309 IN COMPLEX WITH NAD, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TRP-24; ASP-51 AND ASN-310.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF074484 Genomic DNA. Translation: AAC25601.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JEZ	X-ray	2.20	A/B	1-322	[»]
1K8C	X-ray	2.10	A/B/C/D	1-322	[»]
1MI3	X-ray	1.80	A/B/C/D	1-322	[»]
1R38	X-ray	2.20	A/B/C/D	1-322	[»]
1SM9	X-ray	2.20	A/B/C/D	1-322	[»]
1YE4	X-ray	2.40	A/B/C/D	1-322	[»]
1YE6	X-ray	2.30	A/B/C/D	1-322	[»]
1Z9A	X-ray	2.40	A/B/C/D	2-322	[»]

ProteinModelPortal

O74237.

SMR

O74237. Positions 4-322.

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]

Gene3D

G3DSA:3.20.20.100. Aldo/ket_red. 1 hit.

PANTHER

PTHR11732. Aldo/ket_red. 1 hit.

Pfam

PF00248. Aldo_ket_red. 1 hit.
[Graphical view]

PIRSF

PIRSF000097. AKR. 1 hit.

PRINTS

PR00069. ALDKETRDTASE.

SUPFAM

SSF51430. Aldo/ket_red. 1 hit.

PROSITE

PS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]

ProtoNet

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Entry information

Entry name

XYL1_CANTE

Accession

Primary (citable) accession number: O74237

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	November 1, 1998
Last modified:	June 28, 2011
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program