1zmx: Difference between revisions
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|PDB= 1zmx |SIZE=350|CAPTION= <scene name='initialview01'>1zmx</scene>, resolution 3.10Å | |PDB= 1zmx |SIZE=350|CAPTION= <scene name='initialview01'>1zmx</scene>, resolution 3.10Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=THM:THYMIDINE'>THM</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= dnk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]) | |GENE= dnk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1j90|1J90]], [[1ot3|1OT3]], [[1oe0|1OE0]], [[1zm7|1ZM7]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zmx OCA], [http://www.ebi.ac.uk/pdbsum/1zmx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zmx RCSB]</span> | |||
}} | }} | ||
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[[Category: Skovgaard, T.]] | [[Category: Skovgaard, T.]] | ||
[[Category: Welin, M.]] | [[Category: Welin, M.]] | ||
[[Category: dnk]] | [[Category: dnk]] | ||
[[Category: drosophila melanogaster]] | [[Category: drosophila melanogaster]] | ||
[[Category: n64d mutant]] | [[Category: n64d mutant]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:38:56 2008'' | ||
Revision as of 01:38, 31 March 2008
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| , resolution 3.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | dnk (Drosophila melanogaster) | ||||||
| Activity: | Deoxynucleoside kinase, with EC number 2.7.1.145 | ||||||
| Related: | 1J90, 1OT3, 1OE0, 1ZM7
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of D. melanogaster deoxyribonucleoside kinase N64D mutant in complex with thymidine
OverviewOverview
The Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) double mutant N45D/N64D was identified during a previous directed evolution study. This mutant enzyme had a decreased activity towards the natural substrates and decreased feedback inhibition with dTTP, whereas the activity with 3'-modified nucleoside analogs like 3'-azidothymidine (AZT) was nearly unchanged. Here, we identify the mutation N64D as being responsible for these changes. Furthermore, we crystallized the mutant enzyme in the presence of one of its substrates, thymidine, and the feedback inhibitor, dTTP. The introduction of the charged Asp residue appears to destabilize the LID region (residues 167-176) of the enzyme by electrostatic repulsion and no hydrogen bond to the 3'-OH is made in the substrate complex by Glu172 of the LID region. This provides a binding space for more bulky 3'-substituents like the azido group in AZT but influences negatively the interactions between Dm-dNK, substrates and feedback inhibitors based on deoxyribose. The detailed picture of the structure-function relationship provides an improved background for future development of novel mutant suicide genes for Dm-dNK-mediated gene therapy.
About this StructureAbout this Structure
1ZMX is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D., Welin M, Skovgaard T, Knecht W, Zhu C, Berenstein D, Munch-Petersen B, Piskur J, Eklund H, FEBS J. 2005 Jul;272(14):3733-42. PMID:16008571
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