Structure of PDB 5dia Chain A Binding Site BS01

Receptor Information

>5dia Chain A (length=273) Species: 9606 (Homo sapiens)

PLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPN
GTRVPMEVVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDF
ITERGALQEELARSFFWQVLEAVRHCHNCGVLHRDIKDENILIDLNRGEL
KLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILL
YDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRWCLALRPSDRPTFE
EIQNHPWMQDVLLPQETAEIHLH

Ligand information

• Ligand ID: 5E6
• InChI: InChI=1S/C22H23N7/c23-15-5-1-6-16(10-15)26-21-8-2-7-18(27-21)22-17-11-19(14-4-3-9-24-12-14)25-13-20(17)28-29-22/h2-4,7-9,11-13,15-16H,1,5-6,10,23H2,(H,26,27)(H,28,29)/t15-,16-/m0/s1
• InChIKey: FWMVELRLCYRLLJ-HOTGVXAUSA-N
• SMILES:
  CACTVS 3.385: N[C@H]1CCC[C@@H](C1)Nc2cccc(n2)c3n[nH]c4cnc(cc34)c5cccnc5
  CACTVS 3.385: N[CH]1CCC[CH](C1)Nc2cccc(n2)c3n[nH]c4cnc(cc34)c5cccnc5
  ACDLabs 12.01: C1CCC(N)CC1Nc2cccc(n2)c5c4cc(c3cccnc3)ncc4nn5
  OpenEye OEToolkits 1.9.2: c1cc(nc(c1)NC2CCCC(C2)N)c3c4cc(ncc4[nH]n3)c5cccnc5
  OpenEye OEToolkits 1.9.2: c1cc(nc(c1)N[C@H]2CCC[C@@H](C2)N)c3c4cc(ncc4[nH]n3)c5cccnc5
• Formula: C22 H23 N7
• Name: (1S,3S)-N-{6-[5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]pyridin-2-yl}cyclohexane-1,3-diamine
• ChEMBL: CHEMBL3903896
• ZINC: ZINC000205245815
• PDB chain: 5dia Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5dia Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors.
• Resolution: 1.964 Å
• Binding residue (original residue number in PDB): L44 F49 A65 K67 L120 V126 D128 L174 I185 D186
• Binding residue (residue number reindexed from 1): L12 F17 A33 K35 L88 V94 D96 L142 I153 D154
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=10.46,Ki=0.035nM
  BindingDB: Ki=0.397nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D167 K169 N172 D186 L193 T204
• Catalytic site (residue number reindexed from 1): D135 K137 N140 D154 L161 T172
• Enzyme Commision number: 2.7.11.1: non-specific serine/threonine protein kinase.

Gene Ontology

Molecular Function

• GO:0004672 protein kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0008134 transcription factor binding
• GO:0030145 manganese ion binding
• GO:0043024 ribosomal small subunit binding
• GO:0044024 histone H2AS1 kinase activity
• GO:0046872 metal ion binding
• GO:0106310 protein serine kinase activity

Biological Process

• GO:0006338 chromatin remodeling
• GO:0006468 protein phosphorylation
• GO:0006915 apoptotic process
• GO:0016310 phosphorylation
• GO:0022898 regulation of transmembrane transporter activity
• GO:0043066 negative regulation of apoptotic process
• GO:0043433 negative regulation of DNA-binding transcription factor activity
• GO:0045824 negative regulation of innate immune response
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0046777 protein autophosphorylation
• GO:0050821 protein stabilization
• GO:0060045 positive regulation of cardiac muscle cell proliferation
• GO:0070561 vitamin D receptor signaling pathway
• GO:0071346 cellular response to type II interferon
• GO:0090336 positive regulation of brown fat cell differentiation
• GO:1902033 regulation of hematopoietic stem cell proliferation
• GO:1904263 positive regulation of TORC1 signaling
• GO:1905062 positive regulation of cardioblast proliferation
• GO:1990748 cellular detoxification

Cellular Component

• GO:0005634 nucleus
• GO:0005654 nucleoplasm
• GO:0005730 nucleolus
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005886 plasma membrane

External links

• PDB: RCSB:5dia, PDBe:5dia, PDBj:5dia
• PDBsum: 5dia
• PubMed: 26459208
• UniProt: P11309|PIM1_HUMAN Serine/threonine-protein kinase pim-1 (Gene Name=PIM1)