O76290 (O76290_TRYBB) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names

Submitted name:
Pteridine reductase EMBL AAC23562.1

Gene names

Name:

PTR1 EMBL AAC23562.1

Organism

Trypanosoma brucei brucei EMBL AAC23562.1

Taxonomic identifier

5702 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma › Trypanozoon › Trypanosoma brucei

Protein attributes

Sequence length	268 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

Ontologies

Keywords
Ligand	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2 Nucleotide-binding PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
Technical term	3D-structure PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 2YHU PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
Gene Ontology (GO)
Biological_process	oxidation-reduction process Inferred from electronic annotation. Source: GOC
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Regions
	Nucleotide binding	14 – 15	2	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Nucleotide binding	35 – 37	3	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Nucleotide binding	62 – 64	3	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Nucleotide binding	93 – 95	3	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Nucleotide binding	204 – 208	5	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Region	95 – 97	3	Methotrexate binding PDB 2C7V
Sites
	Active site	161	1	Proton donor/acceptor PDB 2C7V
	Active site	174	1	Proton donor/acceptor PDB 2C7V
	Binding site	14	1	Methotrexate PDB 2C7V
	Binding site	14	1	Substrate PDB 2C7V
	Binding site	174	1	Methotrexate PDB 2C7V
	Binding site	174	1	NADP PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3GN1 PDB 3MCV PDB 3GN2
	Binding site	178	1	NADP PDB 2C7V PDB 2VZ0 PDB 2WD7 PDB 2WD8 PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 2X9G PDB 2X9N PDB 2X9V PDB 3GN1 PDB 3MCV PDB 3GN2
	Binding site	217	1	Methotrexate PDB 2C7V
	Binding site	221	1	Methotrexate PDB 2C7V
Amino acid modifications
	Modified residue	59	1	Cysteine sulfenic acid (-SOH) PDB 2WD7
	Modified residue	168	1	Cysteine sulfenic acid (-SOH) PDB 2YHU PDB 3BMC PDB 3BMN PDB 3BMO PDB 3BMQ PDB 3GN1

Sequences

	Sequence		Length	Mass (Da)
	O76290 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 346C8257BDC9DD3D	FASTA	268	28,470
	10 20 30 40 50 60 MEAPAAVVTG AAKRIGRAIA VKLHQTGYRV VIHYHNSAEA AVSLADELNK ERSNTAVVCQ 70 80 90 100 110 120 ADLTNSNVLP ASCEEIINSC FRAFGRCDVL VNNASAFYPT PLVQGDHEDN SNGKTVETQV 130 140 150 160 170 180 AELIGTNAIA PFLLTMSFAQ RQKGTNPNCT SSNLSIVNLC DAMVDQPCMA FSLYNMGKHA 190 200 210 220 230 240 LVGLTQSAAL ELAPYGIRVN GVAPGVSLLP VAMGEEEKDK WRRKVPLGRR EASAEQIADA 250 260 VIFLVSGSAQ YITGSIIKVD GGLSLVHA

References

[1]	Detke S. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE.
[2]	"Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate." Dawson A., Gibellini F., Sienkiewicz N., Tulloch L.B., Fyfe P.K., McLuskey K., Fairlamb A.H., Hunter W.N. Mol. Microbiol. 61:1457-1468(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND NADP, ACTIVE SITE.
[3]	"One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening." Mpamhanga C.P., Spinks D., Tulloch L.B., Shanks E.J., Robinson D.A., Collie I.T., Fairlamb A.H., Wyatt P.G., Frearson J.A., Hunter W.N., Gilbert I.H., Brenk R. J. Med. Chem. 52:4454-4465(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH NADP, CYSTEINE SULFENIC ACID (-SOH) AT CYS-59 AND CYS-168.
[4]	"High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target." Dawson A., Tulloch L.B., Barrack K.L., Hunter W.N. Acta Crystallogr. D 66:1334-1340(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) IN COMPLEX WITH NADP.
[5]	"Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase." Shanks E.J., Ong H.B., Robinson D.A., Thompson S., Sienkiewicz N., Fairlamb A.H., Frearson J.A. Anal. Biochem. 396:194-203(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH NADP.
[6]	"Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases." Tulloch L.B., Martini V.P., Iulek J., Huggan J.K., Lee J.H., Gibson C.L., Smith T.K., Suckling C.J., Hunter W.N. J. Med. Chem. 53:221-229(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH NADP, CYSTEINE SULFENIC ACID (-SOH) AT CYS-168.
[7]	"Structural Studies of Thiadiazole Derivatives that Inhibit Trypanosoma Brucei Growth." Nerini E., Dawson A., Hannaert V., Michels P.A., Hunter W.N., Costi M.P. Submitted (MAY-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS), CYSTEINE SULFENIC ACID (-SOH) AT CYS-168.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF049903 mRNA. Translation: AAC23562.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C7V	X-ray	2.20	A/B/C/D	1-268	[»]
2VZ0	X-ray	1.90	A/B/C/D	1-268	[»]
2WD7	X-ray	1.90	A/B/C/D	1-268	[»]
2WD8	X-ray	2.10	A/B/C/D	1-268	[»]
2X9G	X-ray	1.10	A/B/C/D	1-268	[»]
2X9N	X-ray	1.15	A/B/C/D	1-268	[»]
2X9V	X-ray	1.30	A/B/C/D	1-268	[»]
2YHU	X-ray	2.01	A/B/C/D	1-268	[»]
3BMC	X-ray	2.60	A/B/C/D	1-268	[»]
3BMN	X-ray	1.98	A/B/C/D	1-268	[»]
3BMO	X-ray	1.60	A/B/C/D	1-268	[»]
3BMQ	X-ray	1.70	A/B/C/D	1-268	[»]
3GN1	X-ray	2.00	A/B/C/D	1-268	[»]
3GN2	X-ray	1.60	A/B/C/D	1-268	[»]
3MCV	X-ray	1.70	A/B/C/D	1-268	[»]

ProteinModelPortal

O76290.

SMR

O76290. Positions 2-268.

ModBase

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Protein-protein interaction databases

STRING

5691.Tb927.8.2210.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR014058. Pteridine_reductase.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

TIGRFAMs

TIGR02685. pter_reduc_Leis. 1 hit.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

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Other

EvolutionaryTrace

O76290.

Entry information

Entry name

O76290_TRYBB

Accession

Primary (citable) accession number: O76290

Entry history

Integrated into UniProtKB/TrEMBL:	November 1, 1998
Last sequence update:	November 1, 1998
Last modified:	April 3, 2013
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)