1q92
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1q92.gif|left|200px]] | + | [[Image:1q92.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the inhibitor PMcP-U''' | + | {{Structure |
| + | |PDB= 1q92 |SIZE=350|CAPTION= <scene name='initialview01'>1q92</scene>, resolution 1.40Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=DRM:{[(1R,2S)-2-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)CYCLOPENTYL]OXY}METHYLPHOSPHONIC+ACID'>DRM</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the inhibitor PMcP-U''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1Q92 is a [ | + | 1Q92 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q92 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of the mitochondrial deoxyribonucleotidase in complex with two specific inhibitors., Rinaldo-Matthis A, Rampazzo C, Balzarini J, Reichard P, Bianchi V, Nordlund P, Mol Pharmacol. 2004 Apr;65(4):860-7. PMID:[http:// | + | Crystal structures of the mitochondrial deoxyribonucleotidase in complex with two specific inhibitors., Rinaldo-Matthis A, Rampazzo C, Balzarini J, Reichard P, Bianchi V, Nordlund P, Mol Pharmacol. 2004 Apr;65(4):860-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15044615 15044615] |
[[Category: 5'-nucleotidase]] | [[Category: 5'-nucleotidase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 25: | Line 34: | ||
[[Category: alpha-beta rossman fold]] | [[Category: alpha-beta rossman fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:34:31 2008'' |
Revision as of 11:34, 20 March 2008
| |||||||
| , resolution 1.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | 5'-nucleotidase, with EC number 3.1.3.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the inhibitor PMcP-U
Overview
Monophosphate nucleotidases are enzymes that dephosphorylate nucleotides to their corresponding nucleosides. They play potentially important roles in controlling the activation of nucleotide-based drugs targeted against viral infections or cancer cells. The human mitochondrial deoxyribonucleotidase (dNT-2) dephosphorylates thymidine and deoxyuridine monophosphates. We describe the high resolution structures of the dNT-2 enzyme in complex with two potent nucleoside phosphonate inhibitors, (S)-1-[2'-deoxy-3',5'-O-(1-phosphono) benzylidene-beta-d-threo-pentofuranosyl]thymine (DPB-T) at 1.6-A resolution and (+/-)-1-trans-(2-phosphonomethoxycyclopentyl)uracil (PMcP-U) at 1.4-A resolution. The mixed competitive inhibitor DPB-T and the competitive inhibitor PMcP-U both bind in the active site of dNT-2 but in distinctly different binding modes, explaining their different kinetics of inhibition. The pyrimidine part of the inhibitors binds with very similar hydrogen bond interactions to the protein but with their phosphonate moieties in different binding sites compared with each other and to the previously determined position of phosphate bound to dNT-2. Together, these phosphate/phosphonate binding sites describe what might constitute a functionally relevant phosphate entrance tunnel to the active site. The structures of the inhibitors in complex with dNT-2, being the first such complexes of any nucleotidase, might provide important information for the design of more specific inhibitors to control the activation of nucleotide-based drugs.
About this Structure
1Q92 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of the mitochondrial deoxyribonucleotidase in complex with two specific inhibitors., Rinaldo-Matthis A, Rampazzo C, Balzarini J, Reichard P, Bianchi V, Nordlund P, Mol Pharmacol. 2004 Apr;65(4):860-7. PMID:15044615
Page seeded by OCA on Thu Mar 20 13:34:31 2008
