Structure of PDB 4v25 Chain A Binding Site BS01

Receptor Information
>4v25 Chain A (length=343) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSAPKYIEHFSKFSPSPLSMKQFLDFGSACEKTSFTFLRQELPVRLANIM
KEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDA
LVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISI
RMLINQHTLIFDPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDL
EIQEINAANSKQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLILPP
IKVMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPPLAGFGYGLP
ISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVY
Ligand information
Ligand IDTF3
InChIInChI=1S/C20H25ClN2O2/c1-14(2)17-6-3-15(4-7-17)13-25-19-8-5-16(11-18(19)21)12-20(24)23-10-9-22/h3-8,11,14H,9-10,12-13,22H2,1-2H3,(H,23,24)
InChIKeyDFXJYVQAAFOZDP-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 10.04Clc2cc(ccc2OCc1ccc(cc1)C(C)C)CC(=O)NCCN
OpenEye OEToolkits 1.5.0CC(C)c1ccc(cc1)COc2ccc(cc2Cl)CC(=O)NCCN
CACTVS 3.341CC(C)c1ccc(COc2ccc(CC(=O)NCCN)cc2Cl)cc1
FormulaC20 H25 Cl N2 O2
NameN-(2-AMINOETHYL)-2-{3-CHLORO-4-[(4-ISOPROPYLBENZYL)OXY]PHENYL} ACETAMIDE
ChEMBLCHEMBL1236255
DrugBankDB08610
ZINCZINC000016051834
PDB chain4v25 Chain A Residue 1367 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4v25 VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells.
Resolution2.6 Å
Binding residue
(original residue number in PDB)		L63 P64 V67 G125 V126 Y129 N142 I143 F146
Binding residue
(residue number reindexed from 1)		L56 P57 V60 G118 V119 Y122 N135 I136 F139
Annotation score1
Binding affinityBindingDB: IC50=2000nM
Enzymatic activity
Catalytic site (original residue number in PDB) H239 E243 K246 N247
Catalytic site (residue number reindexed from 1) H225 E229 K232 N233
Enzyme Commision number 2.7.11.2: [pyruvate dehydrogenase (acetyl-transferring)] kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0042803 protein homodimerization activity
Biological Process
GO:0006006 glucose metabolic process
GO:0006111 regulation of gluconeogenesis
GO:0006885 regulation of pH
GO:0008286 insulin receptor signaling pathway
GO:0010510 regulation of acetyl-CoA biosynthetic process from pyruvate
GO:0010565 regulation of cellular ketone metabolic process
GO:0010906 regulation of glucose metabolic process
GO:0016310 phosphorylation
GO:0031670 cellular response to nutrient
GO:0034614 cellular response to reactive oxygen species
GO:0042593 glucose homeostasis
GO:0050848 regulation of calcium-mediated signaling
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
Cellular Component
GO:0005654 nucleoplasm
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005829 cytosol
GO:0045254 pyruvate dehydrogenase complex

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4v25, PDBe:4v25, PDBj:4v25
PDBsum4v25
PubMed25404640
UniProtQ15119|PDK2_HUMAN [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (Gene Name=PDK2)

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