Structure of PDB 4v25 Chain A

Receptor sequence
>4v25A (length=343) Species: 9606 (Homo sapiens) [Search protein sequence]
GSAPKYIEHFSKFSPSPLSMKQFLDFGSACEKTSFTFLRQELPVRLANIM
KEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDA
LVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISI
RMLINQHTLIFDPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDL
EIQEINAANSKQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLILPP
IKVMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPPLAGFGYGLP
ISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVY
3D structure
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.
ChainA
Resolution2.6 Å
3D
structure
Catalytic site residues are labeled in the structure
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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.
Interaction with ligand
Site
#		 Ligand Ligand
chain		 Binding residues on receptor
(original residue number in PDB)		 Binding residues on receptor
(residue number reindexed from 1)		 Binding affinity
BS01 TF3 A L63 P64 V67 G125 V126 Y129 N142 I143 F146 L56 P57 V60 G118 V119 Y122 N135 I136 F139 BindingDB: IC50=2000nM
BS02 SZ6 A K246 N247 R250 A251 D282 G284 G286 V287 T346 K232 N233 R236 A237 D268 G270 G272 V273 T323 PDBbind-CN: -logKd/Ki=7.08,IC50=84nM
BindingDB: IC50=80nM
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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