Structure of PDB 4x3v Chain A Binding Site BS02

Receptor Information

>4x3v Chain A (length=714) Species: 9606 (Homo sapiens)

MFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLAAET
AATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGKHS
PMVAKSTLDIVLANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKV
AERPQHMLMRVSVGIHKEDIDAAIETYNLLSERWFTHASPTLFNAGTNRP
QLSSCFLLSMKDDSIEGIYDTLKQCALISKSAGGIGVAVSCIRATGSYIA
GTNGNSNGLVPMLRVYNNTARYVDQGAFAIYLEPWHLDIFEFLDLKKRDL
FFALWIPDLFMKRVETNQDWSLMCPNECPGLDEVWGEEFEKLYASYEKQG
RVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNLGTIKCSNL
CTEIVEYTSKDEVAVCNLASLALNMYVTSEHTYDFKKLAEVTKVVVRNLN
KIIDINYYPVPEACLSNKRHRPIGIGVQGLADAFILMRYPFESAEAQLLN
KQIFETIYYGALEASCDLAKEQGPYETYEGSPVSKGILQYDMWNVTPTDL
WDWKVLKEKIAKYGIRNSLLIAPMPTASTAQILGNNESIEPYTSNIYTRR
VLSGEFQIVNPHLLKDLTERGLWHEEMKNQIIACNGSIQSIPEIPDDLKQ
LYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKLTSMHFYGW
KQGLKTGMYYLRTR

Ligand information

• Ligand ID: 3X4
• InChI: InChI=1S/C20H26N4O6/c1-20(2,19(30)22-10-6-5-9-14(21)18(28)29)23-15(25)11-24-16(26)12-7-3-4-8-13(12)17(24)27/h3-4,7-8,14H,5-6,9-11,21H2,1-2H3,(H,22,30)(H,23,25)(H,28,29)/t14-/m1/s1
• InChIKey: HSKHXKLBWCBTSW-CQSZACIVSA-N
• SMILES:
  CACTVS 3.385: CC(C)(NC(=O)CN1C(=O)c2ccccc2C1=O)C(=O)NCCCC[C@@H](N)C(O)=O
  ACDLabs 12.01: C(C(NCCCCC(C(O)=O)N)=O)(NC(=O)CN2C(=O)c1ccccc1C2=O)(C)C
  OpenEye OEToolkits 1.9.2: CC(C)(C(=O)NCCCC[C@H](C(=O)O)N)NC(=O)CN1C(=O)c2ccccc2C1=O
  CACTVS 3.385: CC(C)(NC(=O)CN1C(=O)c2ccccc2C1=O)C(=O)NCCCC[CH](N)C(O)=O
  OpenEye OEToolkits 1.9.2: CC(C)(C(=O)NCCCCC(C(=O)O)N)NC(=O)CN1C(=O)c2ccccc2C1=O
• Formula: C20 H26 N4 O6
• Name: N~6~-{N-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl]-2-methyl-D-alanyl}-D-lysine
• ZINC: ZINC000263620531
• PDB chain: 4x3v Chain A Residue 802

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): Y48 S49
• Binding residue (residue number reindexed from 1): Y35 S36
• 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): C205 N399 C401 E403 C416 Y709 Y710
• 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)