Structure of PDB 4bzn Chain A Binding Site BS01

Receptor Information

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

PLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPN
GTRVPMEVVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDF
ITERGALQEELARSFFWQVLEAVRHCHNCGVLHRDIKDENILIDLNRGEL
KLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILL
YDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRWCLALRPSDRPTFE
EIQNHPWMQDVLLPQETAEIHLH

Ligand information

• Ligand ID: UGX
• InChI: InChI=1S/C18H23N3O2S/c1-18(2,3)11-20-16(22)7-14-8-19-17(23)15-6-13(9-21(14)15)12-4-5-24-10-12/h4-6,9-10,14H,7-8,11H2,1-3H3,(H,19,23)(H,20,22)/t14-/m0/s1
• InChIKey: PNMQDIXULZYDDT-AWEZNQCLSA-N
• SMILES:
  CACTVS 3.385: CC(C)(C)CNC(=O)C[CH]1CNC(=O)c2cc(cn12)c3cscc3
  ACDLabs 12.01: O=C3c2n(cc(c1ccsc1)c2)C(CC(=O)NCC(C)(C)C)CN3
  CACTVS 3.385: CC(C)(C)CNC(=O)C[C@H]1CNC(=O)c2cc(cn12)c3cscc3
  OpenEye OEToolkits 1.9.2: CC(C)(C)CNC(=O)CC1CNC(=O)c2n1cc(c2)c3ccsc3
  OpenEye OEToolkits 1.9.2: CC(C)(C)CNC(=O)C[C@H]1CNC(=O)c2n1cc(c2)c3ccsc3
• Formula: C18 H23 N3 O2 S
• Name: N-(2,2-dimethylpropyl)-2-[1-oxo-7-(thiophen-3-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl]acetamide
• ZINC: ZINC000095920975
• PDB chain: 4bzn Chain A Residue 1306

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4bzn Discovery and Optimization of Pyrrolo[1,2-A]Pyrazinones Leads to Novel and Selective Inhibitors of Pim Kinases.
• Resolution: 1.9 Å
• Binding residue (original residue number in PDB): G45 F49 V52 A65 K67 L120 R122 D128 L174 I185 D186
• Binding residue (residue number reindexed from 1): G13 F17 V20 A33 K35 L88 R90 D96 L142 I153 D154
• Annotation score: 1
• Binding affinity: MOAD: ic50=1.441uM
  PDBbind-CN: -logKd/Ki=5.84,IC50=1.441uM
  BindingDB: IC50=1441nM

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