1gy3: Difference between revisions
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[[Image:1gy3. | [[Image:1gy3.jpg|left|200px]]<br /><applet load="1gy3" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1gy3" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1gy3, resolution 2.7Å" /> | caption="1gy3, resolution 2.7Å" /> | ||
'''PCDK2/CYCLIN A IN COMPLEX WITH MGADP, NITRATE AND PEPTIDE SUBSTRATE'''<br /> | '''PCDK2/CYCLIN A IN COMPLEX WITH MGADP, NITRATE AND PEPTIDE SUBSTRATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1GY3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, NO3, ATP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. | 1GY3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, NO3, ATP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:No3 Binding Site For Chain C'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GY3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thr160-phospho-cyclin dependent protein kinase 2 in association with cyclin a]] | [[Category: thr160-phospho-cyclin dependent protein kinase 2 in association with cyclin a]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 15:44:55 2007'' | ||
Revision as of 16:35, 18 December 2007
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PCDK2/CYCLIN A IN COMPLEX WITH MGADP, NITRATE AND PEPTIDE SUBSTRATE
OverviewOverview
Eukaryotic protein kinases catalyze the phosphoryl transfer of the, gamma-phosphate of ATP to the serine, threonine, or tyrosine residue of, protein substrates. The catalytic mechanism of phospho-CDK2/cyclin A, (pCDK2/cyclin A) has been probed with structural and kinetic studies using, the trigonal NO(3)(-) ion, which can be viewed as a mimic of the, metaphosphate transition state. The crystal structure of pCDK2/cyclin A in, complex with Mg(2+)ADP, nitrate, and a heptapeptide substrate has been, determined at 2.7 A. The nitrate ion is located between the beta-phosphate, of ADP and the hydroxyl group of the serine residue of the substrate. In, one molecule of the asymmetric unit, the nitrate is close to the, beta-phosphate of ADP (distance from the nitrate nitrogen to the nearest, beta-phosphate oxygen of 2.5 A), while in the other subunit, the nitrate, is closer to the substrate serine (distance of 2.1 A). Kinetic studies, demonstrate that nitrate is not an effective inhibitor of protein kinases, consistent with the structural results that show the nitrate ion makes few, stabilizing interactions with CDK2 at the catalytic site. The binding of, orthovanadate was also investigated as a mimic of a pentavalent, phosphorane intermediate of an associative mechanism for phosphoryl, transfer. No vanadate was observed bound in a 3.4 A resolution structure, of pCDK2/cyclin A in the presence of Mg(2+)ADP, and vanadate did not, inhibit the kinase reaction. The results support the notion that the, protein kinase reaction proceeds through a mostly dissociative mechanism, with a trigonal planar metaphosphate intermediate rather than an, associative mechanism that involves a pentavalent phosphorane, intermediate.
About this StructureAbout this Structure
1GY3 is a Protein complex structure of sequences from Homo sapiens with MG, NO3, ATP and GOL as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state analogue: implications for the protein kinase mechanism., Cook A, Lowe ED, Chrysina ED, Skamnaki VT, Oikonomakos NG, Johnson LN, Biochemistry. 2002 Jun 11;41(23):7301-11. PMID:12044161
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