Structure of PDB 4x3v Chain B Binding Site BS01

Receptor Information

>4x3v Chain B (length=738) Species: 9606 (Homo sapiens)

MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSG
VTTVELDTLAAETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMED
LYNYINPHNGKHSPMVAKSTLDIVLANKDRLNSAIIYDRDFSYNYFGFKT
LERSYLLKINGKVAERPQHMLMRVSVGIHKEDIDAAIETYNLLSERWFTH
ASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCALISKSAGGIGV
AVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNPGAFAIYLE
PWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMC
PNECPGLDEVWGEEFEKLYASYEKQGRVRKVVKAQQLWYAIIESQTETGT
PYMLYKDSCNRKSNQQNLGTIKCSNLCTEIVEYTSKDEVAVCNLASLALN
MYVTSEHTYDFKKLAEVTKVVVRNLNKIIDINYYPVPEACLSNKRHRPIG
IGVQGLADAFILMRYPFESAEAQLLNKQIFETIYYGALEASCDLAKEQGP
YETYEGSPVSKGILQYDMWNVTPTDLWDWKVLKEKIAKYGIRNSLLIAPM
PTASTAQILGNNESIEPYTSNIYTRRVGEFQIVNPHLLKDLTERGLWHEE
MKNQIIACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQ
SQSLNIHIAEPNYGKLTSMHFYGWKQGLKTGMYYLRTR

Ligand information

• Ligand ID: TTP
• InChI: InChI=1S/C10H17N2O14P3/c1-5-3-12(10(15)11-9(5)14)8-2-6(13)7(24-8)4-23-28(19,20)26-29(21,22)25-27(16,17)18/h3,6-8,13H,2,4H2,1H3,(H,19,20)(H,21,22)(H,11,14,15)(H2,16,17,18)/t6-,7+,8+/m0/s1
• InChIKey: NHVNXKFIZYSCEB-XLPZGREQSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)CO[P@](=O)(O)O[P@@](=O)(O)OP(=O)(O)O)O
  CACTVS 3.341: CC1=CN([CH]2C[CH](O)[CH](CO[P](O)(=O)O[P](O)(=O)O[P](O)(O)=O)O2)C(=O)NC1=O
  ACDLabs 10.04: O=P(O)(O)OP(=O)(O)OP(=O)(O)OCC2OC(N1C(=O)NC(=O)C(=C1)C)CC2O
  OpenEye OEToolkits 1.5.0: CC1=CN(C(=O)NC1=O)C2CC(C(O2)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O
  CACTVS 3.341: CC1=CN([C@H]2C[C@H](O)[C@@H](CO[P@@](O)(=O)O[P@](O)(=O)O[P](O)(O)=O)O2)C(=O)NC1=O
• Formula: C10 H17 N2 O14 P3
• Name: THYMIDINE-5'-TRIPHOSPHATE
• ChEMBL: CHEMBL363559
• DrugBank: DB02452
• ZINC: ZINC000008215959
• PDB chain: 4x3v Chain A Residue 801

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4x3v Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators.
• Resolution: 3.7 Å
• Binding residue (original residue number in PDB): K243 Y285
• Binding residue (residue number reindexed from 1): K243 Y285
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): C218 N427 C429 E431 C444 Y737 Y738
• Catalytic site (residue number reindexed from 1): C218 N425 C427 E429 C442 Y733 Y734
• Enzyme Commision number: 1.17.4.1: ribonucleoside-diphosphate reductase.

Gene Ontology

Molecular Function

• GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0016491 oxidoreductase activity
• GO:0017076 purine nucleotide binding
• GO:0042802 identical protein binding
• GO:0061731 ribonucleoside-diphosphate reductase activity
• GO:0097718 disordered domain specific binding

Biological Process

• GO:0000731 DNA synthesis involved in DNA repair
• GO:0006206 pyrimidine nucleobase metabolic process
• GO:0006264 mitochondrial DNA replication
• GO:0006281 DNA repair
• GO:0008584 male gonad development
• GO:0009185 ribonucleoside diphosphate metabolic process
• GO:0009263 deoxyribonucleotide biosynthetic process
• GO:0009265 2'-deoxyribonucleotide biosynthetic process
• GO:0010212 response to ionizing radiation
• GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
• GO:0021846 cell proliferation in forebrain
• GO:0051290 protein heterotetramerization
• GO:0060041 retina development in camera-type eye
• GO:0070318 positive regulation of G0 to G1 transition
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle

Cellular Component

• GO:0005635 nuclear envelope
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005829 cytosol
• GO:0005971 ribonucleoside-diphosphate reductase complex
• GO:0042995 cell projection
• GO:0043025 neuronal cell body

External links

• PDB: RCSB:4x3v, PDBe:4x3v, PDBj:4x3v
• PDBsum: 4x3v
• PubMed: 26488902
• UniProt: P23921|RIR1_HUMAN Ribonucleoside-diphosphate reductase large subunit (Gene Name=RRM1)