1z4j
From Proteopedia
(New page: 200px<br /> <applet load="1z4j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z4j, resolution 1.80Å" /> '''Structure of the D4...) |
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| - | [[Image:1z4j.gif|left|200px]]<br /> | + | [[Image:1z4j.gif|left|200px]]<br /><applet load="1z4j" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1z4j, resolution 1.80Å" /> | caption="1z4j, resolution 1.80Å" /> | ||
'''Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex with uridine 2'-monophosphate'''<br /> | '''Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex with uridine 2'-monophosphate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The human mitochondrial deoxyribonucleotidase catalyzes the | + | The human mitochondrial deoxyribonucleotidase catalyzes the dephosphorylation of thymidine and deoxyuridine monophosphates and participates in the regulation of the dTTP pool in mitochondria. We present seven structures of the inactive D41N variant of this enzyme in complex with thymidine 3'-monophosphate, thymidine 5'-monophosphate, deoxyuridine 5'-monophosphate, uridine 5'-monophosphate, deoxyguanosine 5'-monophosphate, uridine 2'-monophosphate, and the 5'-monophosphate of the nucleoside analog 3'-deoxy 2'3'-didehydrothymidine, and we draw conclusions about the substrate specificity based on comparisons with enzyme activities. We show that the enzyme's specificity for the deoxyribo form of nucleoside 5'-monophosphates is due to Ile-133, Phe-49, and Phe-102, which surround the 2' position of the sugar and cause an energetically unfavorable environment for the 2'-hydroxyl group of ribonucleoside 5'-monophosphates. The close binding of the 3'-hydroxyl group of nucleoside 5'-monophosphates to the enzyme indicates that nucleoside analog drugs that are substituted with a bulky group at this position will not be good substrates for this enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z4J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, U2P and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1Z4J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=U2P:'>U2P</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z4J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: alfa beta fold]] | [[Category: alfa beta fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:02 2008'' |
Revision as of 14:12, 21 February 2008
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Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex with uridine 2'-monophosphate
Overview
The human mitochondrial deoxyribonucleotidase catalyzes the dephosphorylation of thymidine and deoxyuridine monophosphates and participates in the regulation of the dTTP pool in mitochondria. We present seven structures of the inactive D41N variant of this enzyme in complex with thymidine 3'-monophosphate, thymidine 5'-monophosphate, deoxyuridine 5'-monophosphate, uridine 5'-monophosphate, deoxyguanosine 5'-monophosphate, uridine 2'-monophosphate, and the 5'-monophosphate of the nucleoside analog 3'-deoxy 2'3'-didehydrothymidine, and we draw conclusions about the substrate specificity based on comparisons with enzyme activities. We show that the enzyme's specificity for the deoxyribo form of nucleoside 5'-monophosphates is due to Ile-133, Phe-49, and Phe-102, which surround the 2' position of the sugar and cause an energetically unfavorable environment for the 2'-hydroxyl group of ribonucleoside 5'-monophosphates. The close binding of the 3'-hydroxyl group of nucleoside 5'-monophosphates to the enzyme indicates that nucleoside analog drugs that are substituted with a bulky group at this position will not be good substrates for this enzyme.
About this Structure
1Z4J is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for substrate specificity of the human mitochondrial deoxyribonucleotidase., Wallden K, Ruzzenente B, Rinaldo-Matthis A, Bianchi V, Nordlund P, Structure. 2005 Jul;13(7):1081-8. PMID:16004879
Page seeded by OCA on Thu Feb 21 16:12:02 2008
Categories: Homo sapiens | Single protein | Bianchi, V. | Nordlund, P. | Rinaldo-Matthis, A. | Ruzzenente, B. | Wallden, K. | GOL | MG | U2P | Alfa beta fold
