O15909 · RIR1_TRYBB
- ProteinRibonucleoside-diphosphate reductase large subunit
- GeneRNR1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids838 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Provides the precursors necessary for DNA synthesis. Catalyzes the rate limiting step in the de novo synthesis of deoxyribonucleotides by directly reducing ribonucleotides to the corresponding deoxyribonucleotides.
Catalytic activity
- [thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-diphosphateThis reaction proceeds in the backward direction.
RHEA-COMP:10700 CHEBI:50058 Position: n/n+3+ CHEBI:73316 + CHEBI:15377 = RHEA-COMP:10698 CHEBI:29950 Position: nCHEBI:29950 Position: n+3+ CHEBI:57930
Activity 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.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 10-11 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: KR | ||||||
Binding site | 16-22 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: EPYDEKV | ||||||
Binding site | 58 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 62 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: D | ||||||
Binding site | 227 | GDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Site | 228 | Important for hydrogen atom transfer | ||||
Sequence: C | ||||||
Binding site | 236-238 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: DSI | ||||||
Binding site | 253 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: K | ||||||
Binding site | 266 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: R | ||||||
Binding site | 273-274 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: AG | ||||||
Active site | 437 | Proton acceptor | ||||
Sequence: N | ||||||
Binding site | 437 | GDP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 439 | Cysteine radical intermediate | ||||
Sequence: C | ||||||
Active site | 441 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 441 | GDP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 454 | Important for hydrogen atom transfer | ||||
Sequence: C | ||||||
Binding site | 626-629 | GDP (UniProtKB | ChEBI) | ||||
Sequence: TAST | ||||||
Site | 759 | Important for electron transfer | ||||
Sequence: Y | ||||||
Site | 760 | Important for electron transfer | ||||
Sequence: Y | ||||||
Site | 833 | Interacts with thioredoxin/glutaredoxin | ||||
Sequence: C | ||||||
Site | 836 | Interacts with thioredoxin/glutaredoxin | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | nucleoplasm | |
Cellular Component | ribonucleoside-diphosphate reductase complex | |
Molecular Function | ATP binding | |
Molecular Function | ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor | |
Biological Process | deoxyribonucleotide biosynthetic process | |
Biological Process | DNA replication |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRibonucleoside-diphosphate reductase large subunit
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Discoba > Euglenozoa > Kinetoplastea > Metakinetoplastina > Trypanosomatida > Trypanosomatidae > Trypanosoma
Accessions
- Primary accessionO15909
Subcellular Location
UniProt Annotation
GO Annotation
PTM/Processing
Features
Showing features for chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000187199 | 1-838 | Ribonucleoside-diphosphate reductase large subunit | |||
Sequence: MLETVKLVTKRDGSVEPYDEKVVRSRIVNLMSGIDSYYVDVDDLVRVVGEGVREGMSTSMLDELLAETAAYCVTKHPDYGLLAGRLAVTALHKTTTESVLDSFRVLHEHVSQATKRHAPLISEELWDIANKHSAALQQIINYERDFDFEYFGYKTLERSYLLRVHKGRGVMEVVERPQQMFLRVALGIHGEDLERVKETYDYMSQGFFTHATPTLFNAGTPFPQMSSCFLVAMREDSIDGIYDTLKQCAIISKSAGGIGIHMHNIRAAGSYIAGTNGTSNGLVPMLRVWNNTARYVDQGGGKRKGAFAIYLEPWHADIFGFLLLKKNTGKEDQRARDLFYGLWIPDLFMERVESHGTWTLMDPNTAPFLSDCYGQEFTDLYERYEREGRGVRTIQAQELWFLILESQVETGVPFMLYKDACNFKSNQKNLGTIKCSNLCTEIVEYTSRDEVAVCNLASIALPRFVKDGAFDYVALKEVTKVVTRNLNRVIDRNHYPVCEARYSNLRHRPVGIGVQGLADAFALLSLPFAHPEAKKLNRQIFETIYIAAVEASTELAEKDGPYETFKGSPASEGKLQFDLWDEERRIRGMNEDSVHSHCGLWDWDSLKERVVKVGMRNSLLIAPMPTASTSQILGNNECIEPFTSNIYVRRVLSGEFPVVNKHLVKELIRLRLWNDDMRRKIIALNGSVSGIKEIPERIRELYKVVWEIRQKDLIDMAADRGRYIDQSQSLNLFLATPTSSQLTSMHFYSWKKGLKTGMYYLRSQPAADAIKFTLDPKAMKELPKPDKQSKEEVHGSVGRGKRKRVGEKPTANHSNAGAPNLNGPPDTDGDGGCLNCGS | ||||||
Disulfide bond | 228↔454 | Redox-active | ||||
Sequence: CFLVAMREDSIDGIYDTLKQCAIISKSAGGIGIHMHNIRAAGSYIAGTNGTSNGLVPMLRVWNNTARYVDQGGGKRKGAFAIYLEPWHADIFGFLLLKKNTGKEDQRARDLFYGLWIPDLFMERVESHGTWTLMDPNTAPFLSDCYGQEFTDLYERYEREGRGVRTIQAQELWFLILESQVETGVPFMLYKDACNFKSNQKNLGTIKCSNLCTEIVEYTSRDEVAVC |
Keywords
- PTM
Interaction
Subunit
Heterodimer of a large and a small subunit.
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 6-97 | ATP-cone | ||||
Sequence: KLVTKRDGSVEPYDEKVVRSRIVNLMSGIDSYYVDVDDLVRVVGEGVREGMSTSMLDELLAETAAYCVTKHPDYGLLAGRLAVTALHKTTTE | ||||||
Compositional bias | 780-809 | Basic and acidic residues | ||||
Sequence: KELPKPDKQSKEEVHGSVGRGKRKRVGEKP | ||||||
Region | 780-838 | Disordered | ||||
Sequence: KELPKPDKQSKEEVHGSVGRGKRKRVGEKPTANHSNAGAPNLNGPPDTDGDGGCLNCGS |
Sequence similarities
Belongs to the ribonucleoside diphosphate reductase large chain family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length838
- Mass (Da)94,619
- Last updated1998-01-01 v1
- Checksum19A9B95525BAF69A
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 780-809 | Basic and acidic residues | ||||
Sequence: KELPKPDKQSKEEVHGSVGRGKRKRVGEKP |