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1gy3

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[[Image:1gy3.gif|left|200px]]<br />
 
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<applet load="1gy3" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1gy3, resolution 2.7&Aring;" />
 
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'''PCDK2/CYCLIN A IN COMPLEX WITH MGADP, NITRATE AND PEPTIDE SUBSTRATE'''<br />
 
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==Overview==
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==pCDK2/cyclin A in complex with MgADP, nitrate and peptide substrate==
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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.
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<StructureSection load='1gy3' size='340' side='right'caption='[[1gy3]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1gy3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GY3 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gy3 OCA], [https://pdbe.org/1gy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gy3 RCSB], [https://www.ebi.ac.uk/pdbsum/1gy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gy3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CCNA2_HUMAN CCNA2_HUMAN] Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gy/1gy3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gy3 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:12044161</ref>
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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]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GY3 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12044161 12044161]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 1gy3" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Chrysina, E.D.]]
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[[Category: Cook, A.]]
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[[Category: Johnson, L.N.]]
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[[Category: Lowe, E.D.]]
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[[Category: Oikonomakos, N.G.]]
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[[Category: Skamnaki, V.T.]]
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[[Category: ATP]]
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[[Category: GOL]]
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[[Category: MG]]
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[[Category: NO3]]
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[[Category: cell cycle regulatory protein kinase]]
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[[Category: thr160-phospho-cyclin dependent protein kinase 2 in association with cyclin a]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:39:04 2007''
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==See Also==
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*[[Cyclin 3D structures|Cyclin 3D structures]]
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Synthetic construct]]
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[[Category: Chrysina ED]]
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[[Category: Cook A]]
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[[Category: Johnson LN]]
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[[Category: Lowe ED]]
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[[Category: Oikonomakos NG]]
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[[Category: Skamnaki VT]]

Current revision

pCDK2/cyclin A in complex with MgADP, nitrate and peptide substrate

PDB ID 1gy3

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