2r3f: Difference between revisions
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|PDB= 2r3f |SIZE=350|CAPTION= <scene name='initialview01'>2r3f</scene>, resolution 1.50Å | |PDB= 2r3f |SIZE=350|CAPTION= <scene name='initialview01'>2r3f</scene>, resolution 1.50Å | ||
|SITE= <scene name='pdbsite=AC1:Ace+Binding+Site+For+Residue+A+0'>AC1</scene> and <scene name='pdbsite=AC2:Sc8+Binding+Site+For+Residue+A+501'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:Ace+Binding+Site+For+Residue+A+0'>AC1</scene> and <scene name='pdbsite=AC2:Sc8+Binding+Site+For+Residue+A+501'>AC2</scene> | ||
|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene> | |LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=SC8:5-(2,3-DICHLOROPHENYL)-N-(PYRIDIN-4-YLMETHYL)PYRAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>SC8</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </span> | ||
|GENE= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2r3g|2R3G]], [[2r3h|2R3H]], [[2r3i|2R3I]], [[2r3j|2R3J]], [[2r3k|2R3K]], [[2r3l|2R3L]], [[2r3m|2R3M]], [[2r3n|2R3N]], [[2r3o|2R3O]], [[2r3p|2R3P]], [[2r3q|2R3Q]], [[2r3r|2R3R]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3f OCA], [http://www.ebi.ac.uk/pdbsum/2r3f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2r3f RCSB]</span> | |||
}} | }} | ||
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[[Category: Hruza, A W.]] | [[Category: Hruza, A W.]] | ||
[[Category: Madison, V M.]] | [[Category: Madison, V M.]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cancer]] | [[Category: cancer]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:56:08 2008'' | ||
Revision as of 04:56, 31 March 2008
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| , resolution 1.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | , | ||||||
| Gene: | CDK2 (Homo sapiens) | ||||||
| Activity: | Cyclin-dependent kinase, with EC number 2.7.11.22 | ||||||
| Related: | 2R3G, 2R3H, 2R3I, 2R3J, 2R3K, 2R3L, 2R3M, 2R3N, 2R3O, 2R3P, 2R3Q, 2R3R
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor
OverviewOverview
CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity. (c) 2007 Wiley Periodicals, Inc. Biopolymers, 2007.
About this StructureAbout this Structure
2R3F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure-guided discovery of cyclin-dependent kinase inhibitors., Fischmann TO, Hruza A, Duca JS, Ramanathan L, Mayhood T, Windsor WT, Le HV, Guzi TJ, Dwyer MP, Paruch K, Doll RJ, Lees E, Parry D, Seghezzi W, Madison V, Biopolymers. 2007 Oct 15;. PMID:17937404
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