Structure of PDB 4bzo Chain A Binding Site BS01

Receptor Information

>4bzo Chain A (length=273) Species: 9606 (Homo sapiens)

PLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPN
GTRVPMEVVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDF
ITERGALQEELARSFFWQVLEAVRHCHNCGVLHRDIKDENILIDLNRGEL
KLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILL
YDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRWCLALRPSDRPTFE
EIQNHPWMQDVLLPQETAEIHLH

Ligand information

• Ligand ID: 676
• InChI: InChI=1S/C22H22FN5O2/c23-20-9-15(6-7-25-20)16-8-19-22(30)26-12-17(28(19)13-16)10-21(29)27-18(11-24)14-4-2-1-3-5-14/h1-9,13,17-18H,10-12,24H2,(H,26,30)(H,27,29)/t17-,18+/m0/s1
• InChIKey: MCZCAWWHZGEUFE-ZWKOTPCHSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: c1ccc(cc1)C(CN)NC(=O)CC2CNC(=O)c3n2cc(c3)c4ccnc(c4)F
  CACTVS 3.385: NC[C@@H](NC(=O)C[C@H]1CNC(=O)c2cc(cn12)c3ccnc(F)c3)c4ccccc4
  CACTVS 3.385: NC[CH](NC(=O)C[CH]1CNC(=O)c2cc(cn12)c3ccnc(F)c3)c4ccccc4
  OpenEye OEToolkits 1.7.6: c1ccc(cc1)[C@@H](CN)NC(=O)C[C@H]2CNC(=O)c3n2cc(c3)c4ccnc(c4)F
  ACDLabs 12.01: Fc4nccc(c1cn2c(c1)C(=O)NCC2CC(=O)NC(c3ccccc3)CN)c4
• Formula: C22 H22 F N5 O2
• Name: N-[(1S)-2-AMINO-1-PHENYLETHYL]-2-[(4S)-7-(2-FLUORO-4-PYRIDINYL)-1-OXO-1,2,3,4-TETRAHYDROPYRROLO[1,2-A]PYRAZIN-4-YL]ACETAMIDE
• ChEMBL: CHEMBL3298889
• ZINC: ZINC000068204241
• PDB chain: 4bzo Chain A Residue 1306

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4bzo Discovery and Optimization of Pyrrolo[1,2-A]Pyrazinones Leads to Novel and Selective Inhibitors of Pim Kinases.
• Resolution: 2.1 Å
• Binding residue (original residue number in PDB): L44 F49 A65 K67 R122 L174 I185 D186
• Binding residue (residue number reindexed from 1): L12 F17 A33 K35 R90 L142 I153 D154
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.013uM
  PDBbind-CN: -logKd/Ki=7.89,IC50=0.013uM
  BindingDB: IC50=13nM

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:4bzo, PDBe:4bzo, PDBj:4bzo
• PDBsum: 4bzo
• PubMed: 24139169
• UniProt: P11309|PIM1_HUMAN Serine/threonine-protein kinase pim-1 (Gene Name=PIM1)