1ot3: Difference between revisions
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[[Image:1ot3.jpg|left|200px]]<br /><applet load="1ot3" size=" | [[Image:1ot3.jpg|left|200px]]<br /><applet load="1ot3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1ot3, resolution 2.5Å" /> | caption="1ot3, resolution 2.5Å" /> | ||
'''Crystal structure of Drosophila deoxyribonucleotide kinase complexed with the substrate deoxythymidine'''<br /> | '''Crystal structure of Drosophila deoxyribonucleotide kinase complexed with the substrate deoxythymidine'''<br /> | ||
==Overview== | ==Overview== | ||
Deoxyribonucleoside kinases are feedback inhibited by the final products | Deoxyribonucleoside kinases are feedback inhibited by the final products of the salvage pathway, the deoxyribonucleoside triphosphates. In the present study, the mechanism of feedback inhibition is presented based on the crystal structure of a complex between the fruit fly deoxyribonucleoside kinase and its feedback inhibitor deoxythymidine triphosphate. The inhibitor was found to be bound as a bisubstrate inhibitor with its nucleoside part in the nucleoside binding site and with its phosphate groups partially occupying the phosphate donor site. The overall structure of the enzyme--inhibitor complex is very similar to the enzyme--substrate complexes with deoxythymidine and deoxycytidine, except for a conformational change within a region otherwise directly involved in catalysis. This conformational change involves a magnesium ion, which is coordinated in the inhibitor complex to the phosphates and to the primary base, Glu52, that normally is positioned close to the 5'-OH of the substrate deoxyribose. | ||
==About this Structure== | ==About this Structure== | ||
1OT3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with SO4 and THM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Deoxynucleoside_kinase Deoxynucleoside kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.145 2.7.1.145] Full crystallographic information is available from [http:// | 1OT3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=THM:'>THM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Deoxynucleoside_kinase Deoxynucleoside kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.145 2.7.1.145] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OT3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Karlsson, A.]] | [[Category: Karlsson, A.]] | ||
[[Category: Knecht, W.]] | [[Category: Knecht, W.]] | ||
[[Category: Mikkelsen, N | [[Category: Mikkelsen, N E.]] | ||
[[Category: Munch-Petersen, B.]] | [[Category: Munch-Petersen, B.]] | ||
[[Category: Piskur, J.]] | [[Category: Piskur, J.]] | ||
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[[Category: protein-deoxynucleoside complex]] | [[Category: protein-deoxynucleoside complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:21:20 2008'' | ||
Revision as of 15:21, 21 February 2008
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Crystal structure of Drosophila deoxyribonucleotide kinase complexed with the substrate deoxythymidine
OverviewOverview
Deoxyribonucleoside kinases are feedback inhibited by the final products of the salvage pathway, the deoxyribonucleoside triphosphates. In the present study, the mechanism of feedback inhibition is presented based on the crystal structure of a complex between the fruit fly deoxyribonucleoside kinase and its feedback inhibitor deoxythymidine triphosphate. The inhibitor was found to be bound as a bisubstrate inhibitor with its nucleoside part in the nucleoside binding site and with its phosphate groups partially occupying the phosphate donor site. The overall structure of the enzyme--inhibitor complex is very similar to the enzyme--substrate complexes with deoxythymidine and deoxycytidine, except for a conformational change within a region otherwise directly involved in catalysis. This conformational change involves a magnesium ion, which is coordinated in the inhibitor complex to the phosphates and to the primary base, Glu52, that normally is positioned close to the 5'-OH of the substrate deoxyribose.
About this StructureAbout this Structure
1OT3 is a Single protein structure of sequence from Drosophila melanogaster with and as ligands. Active as Deoxynucleoside kinase, with EC number 2.7.1.145 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase., Mikkelsen NE, Johansson K, Karlsson A, Knecht W, Andersen G, Piskur J, Munch-Petersen B, Eklund H, Biochemistry. 2003 May 20;42(19):5706-12. PMID:12741827
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