Structure of PDB 1r78 Chain A Binding Site BS01

Receptor Information

>1r78 Chain A (length=273) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLTAIREISLLKELN
HPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLF
QLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGVTLWYRAPEILL
GCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEV
VWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRI
SAKAALAHPFFQDVTKPVPHLRL

Ligand information

Ligand ID

FMD

InChI

InChI=1S/C20H20FN3O4/c1-10(25)19(22)16(26)6-3-11-13(21)4-5-14-18(11)12(20(27)24-14)9-15-17(28-2)7-8-23-15/h4-5,7-10,16,19,23,25-26H,22H2,1-2H3,(H,24,27)/b12-9-/t10-,16-,19+/m1/s1

InChIKey

RAKYKJWUUUKCCW-MPLBGYFPSA-N

SMILES

Software	SMILES
CACTVS 3.341	COc1cc[nH]c1/C=C/2C(=O)Nc3ccc(F)c(C#C[C@@H](O)[C@@H](N)[C@@H](C)O)c/23
OpenEye OEToolkits 1.5.0	C[C@H]([C@@H]([C@@H](C#Cc1c(ccc2c1/C(=C/c3c(cc[nH]3)OC)/C(=O)N2)F)O)N)O
CACTVS 3.341	COc1cc[nH]c1C=C2C(=O)Nc3ccc(F)c(C#C[CH](O)[CH](N)[CH](C)O)c23
ACDLabs 10.04	Fc1c(C#CC(O)C(N)C(O)C)c\2c(cc1)NC(=O)C/2=C/c3c(OC)ccn3
OpenEye OEToolkits 1.5.0	CC(C(C(C#Cc1c(ccc2c1C(=Cc3c(cc[nH]3)OC)C(=O)N2)F)O)N)O

Formula

C20 H20 F N3 O4

Name

4-((3R,4S,5R)-4-AMINO-3,5-DIHYDROXY-HEX-1-YNYL)-5-FLUORO-3-[1-(3-METHOXY-1H-PYRROL-2-YL)-METH-(Z)-YLIDENE]-1,3-DIHYDRO-INDOL-2-ONE

PDB chain

1r78 Chain A Residue 299 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	1r78 A new series of potent oxindole inhibitors of CDK2
Resolution	2.0 Å
Binding residue (original residue number in PDB)	I10 G11 E12 V18 A31 F80 F82 L83 Q131 L134 D145
Binding residue (residue number reindexed from 1)	I10 G11 E12 V18 A31 F71 F73 L74 Q122 L125 D136
Annotation score	1
Binding affinity	MOAD: ic50=3nM PDBbind-CN: -logKd/Ki=8.52,IC50=3nM BindingDB: IC50=3nM

Enzymatic activity

Catalytic site (original residue number in PDB)	D127 K129 Q131 N132 D145 T165
Catalytic site (residue number reindexed from 1)	D118 K120 Q122 N123 D136 T140
Enzyme Commision number	2.7.11.22: cyclin-dependent kinase.

Gene Ontology

	Molecular Function
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004693	cyclin-dependent protein serine/threonine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0019904	protein domain specific binding
GO:0030332	cyclin binding
GO:0035173	histone kinase activity
GO:0046872	metal ion binding
GO:0097472	cyclin-dependent protein kinase activity
GO:0106310	protein serine kinase activity

	Biological Process
GO:0000082	G1/S transition of mitotic cell cycle
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000122	negative regulation of transcription by RNA polymerase II
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006338	chromatin remodeling
GO:0006351	DNA-templated transcription
GO:0006468	protein phosphorylation
GO:0006813	potassium ion transport
GO:0007099	centriole replication
GO:0007165	signal transduction
GO:0007265	Ras protein signal transduction
GO:0007346	regulation of mitotic cell cycle
GO:0008284	positive regulation of cell population proliferation
GO:0010389	regulation of G2/M transition of mitotic cell cycle
GO:0010468	regulation of gene expression
GO:0016310	phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0031453	positive regulation of heterochromatin formation
GO:0031571	mitotic G1 DNA damage checkpoint signaling
GO:0032298	positive regulation of DNA-templated DNA replication initiation
GO:0043247	telomere maintenance in response to DNA damage
GO:0043687	post-translational protein modification
GO:0045740	positive regulation of DNA replication
GO:0045893	positive regulation of DNA-templated transcription
GO:0051298	centrosome duplication
GO:0051301	cell division
GO:0051321	meiotic cell cycle
GO:0071732	cellular response to nitric oxide
GO:0090398	cellular senescence
GO:1905784	regulation of anaphase-promoting complex-dependent catabolic process

	Cellular Component
GO:0000307	cyclin-dependent protein kinase holoenzyme complex
GO:0000781	chromosome, telomeric region
GO:0000793	condensed chromosome
GO:0000805	X chromosome
GO:0000806	Y chromosome
GO:0001673	male germ cell nucleus
GO:0005634	nucleus
GO:0005635	nuclear envelope
GO:0005654	nucleoplasm
GO:0005667	transcription regulator complex
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0015030	Cajal body
GO:0097123	cyclin A1-CDK2 complex
GO:0097124	cyclin A2-CDK2 complex
GO:0097134	cyclin E1-CDK2 complex
GO:0097135	cyclin E2-CDK2 complex

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Molecular Function

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Biological Process

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Cellular Component

External links

PDB	RCSB:1r78, PDBe:1r78, PDBj:1r78
PDBsum	1r78
PubMed	15012993
UniProt	P24941\|CDK2_HUMAN Cyclin-dependent kinase 2 (Gene Name=CDK2)

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