O15909 (RIR1_TRYBB) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonucleoside-diphosphate reductase large subunit
EC=1.17.4.1

Alternative name(s):
Ribonucleotide reductase R1 subunit

Gene names

Name:

RNR1

Organism

Trypanosoma brucei brucei

Taxonomic identifier

5702 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	838 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
Enzyme regulation	Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the large subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site By similarity.
Pathway	Genetic information processing; DNA replication.
Subunit structure	Heterodimer of a large and a small subunit.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.

Ontologies

Keywords
Biological process	DNA replication
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	Allosteric enzyme
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway deoxyribonucleotide biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	ribonucleoside-diphosphate reductase complex Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 838	838	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187199
Regions
	Domain	6 – 97	92	ATP-cone
	Region	16 – 22	7	Allosteric activator binding By similarity
	Region	227 – 228	2	Substrate binding By similarity
	Region	295 – 298	4	Allosteric effector binding, determines substrate specificity By similarity
	Region	437 – 441	5	Substrate binding By similarity
	Region	625 – 629	5	Substrate binding By similarity
Sites
	Active site	437	1	Proton acceptor By similarity
	Active site	439	1	Cysteine radical intermediate By similarity
	Active site	441	1	Proton acceptor By similarity
	Binding site	10	1	Allosteric activator By similarity
	Binding site	58	1	Allosteric activator By similarity
	Binding site	93	1	Allosteric activator By similarity
	Binding site	212	1	Substrate By similarity
	Binding site	257	1	Substrate; via amide nitrogen By similarity
	Site	228	1	Important for hydrogen atom transfer By similarity
	Site	236	1	Allosteric effector binding, determines substrate specificity By similarity
	Site	266	1	Allosteric effector binding, determines substrate specificity By similarity
	Site	454	1	Important for hydrogen atom transfer By similarity
	Site	759	1	Important for electron transfer By similarity
	Site	760	1	Important for electron transfer By similarity
	Site	833	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	836	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	228 ↔ 454		Redox-active By similarity

Sequences

	Sequence		Length	Mass (Da)
	O15909 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 19A9B95525BAF69A	FASTA	838	94,619
	10 20 30 40 50 60 MLETVKLVTK RDGSVEPYDE KVVRSRIVNL MSGIDSYYVD VDDLVRVVGE GVREGMSTSM 70 80 90 100 110 120 LDELLAETAA YCVTKHPDYG LLAGRLAVTA LHKTTTESVL DSFRVLHEHV SQATKRHAPL 130 140 150 160 170 180 ISEELWDIAN KHSAALQQII NYERDFDFEY FGYKTLERSY LLRVHKGRGV MEVVERPQQM 190 200 210 220 230 240 FLRVALGIHG EDLERVKETY DYMSQGFFTH ATPTLFNAGT PFPQMSSCFL VAMREDSIDG 250 260 270 280 290 300 IYDTLKQCAI ISKSAGGIGI HMHNIRAAGS YIAGTNGTSN GLVPMLRVWN NTARYVDQGG 310 320 330 340 350 360 GKRKGAFAIY LEPWHADIFG FLLLKKNTGK EDQRARDLFY GLWIPDLFME RVESHGTWTL 370 380 390 400 410 420 MDPNTAPFLS DCYGQEFTDL YERYEREGRG VRTIQAQELW FLILESQVET GVPFMLYKDA 430 440 450 460 470 480 CNFKSNQKNL GTIKCSNLCT EIVEYTSRDE VAVCNLASIA LPRFVKDGAF DYVALKEVTK 490 500 510 520 530 540 VVTRNLNRVI DRNHYPVCEA RYSNLRHRPV GIGVQGLADA FALLSLPFAH PEAKKLNRQI 550 560 570 580 590 600 FETIYIAAVE ASTELAEKDG PYETFKGSPA SEGKLQFDLW DEERRIRGMN EDSVHSHCGL 610 620 630 640 650 660 WDWDSLKERV VKVGMRNSLL IAPMPTASTS QILGNNECIE PFTSNIYVRR VLSGEFPVVN 670 680 690 700 710 720 KHLVKELIRL RLWNDDMRRK IIALNGSVSG IKEIPERIRE LYKVVWEIRQ KDLIDMAADR 730 740 750 760 770 780 GRYIDQSQSL NLFLATPTSS QLTSMHFYSW KKGLKTGMYY LRSQPAADAI KFTLDPKAMK 790 800 810 820 830 ELPKPDKQSK EEVHGSVGRG KRKRVGEKPT ANHSNAGAPN LNGPPDTDGD GGCLNCGS

References

[1]	"Cloning and characterization of the R1 and R2 subunits of ribonucleotide reductase from Trypanosoma brucei." Hofer A., Schmidt P.P., Graslund A., Thelander L. Proc. Natl. Acad. Sci. U.S.A. 94:6959-6964(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 427.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U80910 mRNA. Translation: AAB70704.1.
3D structure databases
ProteinModelPortal	O15909.
SMR	O15909. Positions 23-777.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
EuPathDB	TriTrypDB:Tb11.02.5720. TriTrypDB:Tb427tmp.02.5720.
Enzyme and pathway databases
UniPathway	UPA00326.
Family and domain databases
InterPro	IPR005144. ATP-cone. IPR013346. NrdE_NrdA. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. IPR008926. RNR_R1-su_N. [Graphical view]
Pfam	PF03477. ATP-cone. 1 hit. PF02867. Ribonuc_red_lgC. 1 hit. PF00317. Ribonuc_red_lgN. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
SUPFAM	SSF48168. Ribonucleo_red_N. 1 hit.
TIGRFAMs	TIGR02506. NrdE_NrdA. 1 hit.
PROSITE	PS51161. ATP_CONE. 1 hit. PS00089. RIBORED_LARGE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

RIR1_TRYBB

Accession

Primary (citable) accession number: O15909

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)