P50647 (RIR1_PLAFG) 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

Plasmodium falciparum (isolate FCR-3 / Gambia)

Taxonomic identifier

5838 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Laverania) › Plasmodium falciparum

Protein attributes

Sequence length	804 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

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 – 804	804	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187197
Regions
	Domain	1 – 92	92	ATP-cone
	Region	11 – 17	7	Allosteric activator binding By similarity
	Region	216 – 217	2	Substrate binding By similarity
	Region	284 – 287	4	Allosteric effector binding, determines substrate specificity By similarity
	Region	425 – 429	5	Substrate binding By similarity
	Region	602 – 606	5	Substrate binding By similarity
Sites
	Active site	425	1	Proton acceptor By similarity
	Active site	427	1	Cysteine radical intermediate By similarity
	Active site	429	1	Proton acceptor By similarity
	Binding site	53	1	Allosteric activator By similarity
	Binding site	88	1	Allosteric activator By similarity
	Binding site	201	1	Substrate By similarity
	Binding site	246	1	Substrate; via amide nitrogen By similarity
	Site	217	1	Important for hydrogen atom transfer By similarity
	Site	225	1	Allosteric effector binding, determines substrate specificity By similarity
	Site	255	1	Allosteric effector binding, determines substrate specificity By similarity
	Site	442	1	Important for hydrogen atom transfer By similarity
	Site	736	1	Important for electron transfer By similarity
	Site	737	1	Important for electron transfer By similarity
	Site	799	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	802	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	217 ↔ 442		Redox-active By similarity

Sequences

	Sequence		Length	Mass (Da)
	P50647 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 8D3C70EA2ED0A6E9	FASTA	804	92,403
	10 20 30 40 50 60 MYVLNRKGEE EDISFDQILK RIQRLSYGLH KLGEYPACVT QGVINGMYSS IKTCELDELA 70 80 90 100 110 120 AQTCAYMATT HPDFSILAAR ITTDNLHKNT SDDVAEVAEA LYTYKDGRGR PASLISKEVY 130 140 150 160 170 180 DFILLHKVRL NKEIDYTTHF NYDYFGFKTL ERSYLLRINN KIIERPQHLL MRVSIGIHID 190 200 210 220 230 240 DIDKALETYH LMSQKYFTHA TPTLFNSGTP RPQMSSCFLL SMKADSIEGI FETLKQCALI 250 260 270 280 290 300 SKTAGGIGVA VQDIRGQNSY IRGTNGISNG LVPMLRVFND TARYVDQGGG KRKGSYAVYI 310 320 330 340 350 360 EPWHSDIFEF LDLRKNHGKE ELRARDLFYA VWVPDLFMKR VKENKNWTLM CPNECPGLSE 370 380 390 400 410 420 TWGEEFEKLY TKYEEENMGK KTVLAQDLWF AILQSQIETG VPIYLYKDSC NAKPIKNLGT 430 440 450 460 470 480 IKCSNLCCEI IEYTSPDEVA VCNLASIALC KFVDLEKKEF NFKKLYEITK IITRNLDKII 490 500 510 520 530 540 ERNYYPVKEA KTSNTRHRPI GIGVQGLADT FMLLRYLYES DAAKELNKRI YETMYYAALE 550 560 570 580 590 600 MSVDWLQSGP YESYQGSPGS QGILQFDMWN AKVDNKYWDW DELKLKIAKT GLRNLLLLAP 610 620 630 640 650 660 MPTASTSQIL GNNESFEPYT SNIYYRRVLS GEFFVVNPHL LKDLFDRGLW DEDMKQQLIA 670 680 690 700 710 720 HNGSIQYISE IPDDLKELYK TVWEIKQKNI IDMAADRGYF IDQSQSLNIY IQKPTFAKLS 730 740 750 760 770 780 SMHFYGWEKG LKTGAYYLRT QAATDAIKFT VDTHVAKNAV KLKNADGVQI TREVSRETIQ 790 800 LNQRYSKCVS FKSNNDEQCL MCSG

References

[1]

"Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy." Rubin H., Salem J.S., Li L.S., Yang F.D., Mama S., Wang Z.M., Fisher A., Hamann C.S., Cooperman B.S. Proc. Natl. Acad. Sci. U.S.A. 90:9280-9284(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF205580 Genomic DNA. Translation: AAA29755.1.
PIR	B48687.
3D structure databases
ProteinModelPortal	P50647.
SMR	P50647. Positions 15-761.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
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_PLAFG

Accession

Primary (citable) accession number: P50647

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)