P21524D3DLX5RIR1_YEASTRibonucleoside-diphosphate reductase large chain 11.17.4.1Ribonucleotide reductase R1 subunit 1Ribonucleotide reductase large subunit 1RNR1CRT7RIR1SDS12YER070WSaccharomyces cerevisiae (strain ATCC 204508 / S288c)Baker's yeastEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomycesThe nucleotide sequence of Saccharomyces cerevisiae chromosome V.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]GENOME REANNOTATIONTwo genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-100 AND 653-682INDUCTIONUse of synthetic lethal mutants to clone and characterize a novel CTP synthetase gene in Saccharomyces cerevisiae.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 313-384 AND 546-590Yeast Sml1, a protein inhibitor of ribonucleotide reductase.INTERACTION WITH SML1ENZYME REGULATIONYeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit.SUBUNITBIOPHYSICOCHEMICAL PROPERTIESYeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex.FUNCTIONMUTAGENESIS OF CYS-428Global analysis of protein expression in yeast.LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]Subcellular localization of yeast ribonucleotide reductase regulated by the DNA replication and damage checkpoint pathways.SUBCELLULAR LOCATIONQuantitative phosphoproteomics applied to the yeast pheromone signaling pathway.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-816MASS SPECTROMETRYProteome-wide identification of in vivo targets of DNA damage checkpoint kinases.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-816MASS SPECTROMETRYA multidimensional chromatography technology for in-depth phosphoproteome analysis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; SER-809; SER-812; SER-816; SER-837 AND SER-887MASS SPECTROMETRYStructures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation.X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEXES WITH CDP; UDP; TTP; GDP; GTP; ADP AND AMPPNPDISULFIDE BONDStructures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly.X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH GEMCITABINE DIPHOSPHATE AND R2 PEPTIDESSUBUNITThe structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide reductase: a conformationally flexible pharmacophore.X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) IN COMPLEX WITH PEPTIDE INHIBITORSSUBUNITProvides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin.Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the R1 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. Inhibited by SML1.2250 nmol/min/mg enzyme for cytidine 5'-diphosphateOptimum temperature is 30 degrees Celsius.Genetic information processing; DNA replication.Heterotetramer of two large (R1) and two small (R2) subunits. S.cerevisiae has two different R1 subunits (RNR1 and RNR3) and two different R2 subunits (RNR2 and RNR4). The functional form of the small subunits is a RNR2-RNR4 heterodimer, where RNR2 provides the iron-radical center and RNR4 is required for proper folding of RNR2 and assembly with the large subunits. Under normal growth conditions, the active form of the large subunits is a homodimer of the constitutively expressed RNR1. In damaged cells or cells arrested for DNA synthesis, the reductase consists of multiple species because of the association of the small subunits (RNR2-RNR4) with either the RNR1 homodimer or a heterodimer of RNR1 and the damage-inducible RNR3. RNR1 interacts with the ribonucleotide reductase inhibitor SML1.CytoplasmCell cycle-regulated with highest activity in S phase. Moderately induced by DNA-damage.Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on R1, is formed only in the presence of the second subunit R2 (By similarity).Present with 293000 molecules/cell in log phase SD medium.Belongs to the ribonucleoside diphosphate reductase large chain family.Contains 1 ATP-cone domain.3D-structureATP-bindingAllosteric enzymeComplete proteomeCytoplasmDNA replicationDisulfide bondNucleotide-bindingOxidoreductasePhosphoproteinReference proteomeCAFLTLRNLKQEEQ
MYVYKRDGRKEPVQFDKITARISRLCYGLDPKHIDAVKVTQRIISGVYEGVTTIELDNLA
AETCAYMTTVHPDYATLAARIAISNLHKQTTKQFSKVVEDLYRYVNAATGKPAPMISDDV
YNIVMENKDKLNSAIVYDRDFQYSYFGFKTLERSYLLRINGQVAERPQHLIMRVALGIHG
RDIEAALETYNLMSLKYFTHASPTLFNAGTPKPQMSSCFLVAMKEDSIEGIYDTLKECAL
ISKTAGGIGLHIHNIRSTGSYIAGTNGTSNGLIPMIRVFNNTARYVDQGGNKRPGAFALY
LEPWHADIFDFIDIRKNHGKEEIRARDLFPALWIPDLFMKRVEENGTWTLFSPTSAPGLS
DCYGDEFEALYTRYEKEGRGKTIKAQKLWYSILEAQTETGTPFVVYKDACNRKSNQKNLG
VIKSSNLCCEIVEYSAPDETAVCNLASVALPAFIETSEDGKTSTYNFKKLHEIAKVVTRN
LNRVIDRNYYPVEEARKSNMRHRPIALGVQGLADTFMLLRLPFDSEEARLLNIQIFETIY
HASMEASCELAQKDGPYETFQGSPASQGILQFDMWDQKPYGMWDWDTLRKDIMKHGVRNS
LTMAPMPTASTSQILGYNECFEPVTSNMYSRRVLSGEFQVVNPYLLRDLVDLGIWDEGMK
QYLITQNGSIQGLPNVPQELKDLYKTVWEISQKTIINMAADRSVYIDQSHSLNLFLRAPT
MGKLTSMHFYGWKKGLKTGMYYLRTQAASAAIQFTIDQKIADQATENVADISNLKRPSYM
PSSASYAASDFVPAAVTANATIPSLDSSSEASREASPAPTGSHSLTKGMAELNVQESKVE
VPEVPAPTKNEEKAAPIVDDEETEFDIYNSKVIACAIDNPEACEMCSG
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