1e2i: Difference between revisions

Revision as of 14:34, 2 May 2008

THE NUCLEOSIDE BINDING SITE OF HERPES SIMPLEX TYPE 1 THYMIDINE KINASE ANALYZED BY X-RAY CRYSTALLOGRAPHY

OverviewOverview

The crystal structures of the full-length Herpes simplex virus type 1 thymidine kinase in its unligated form and in a complex with an adenine analogue have been determined at 1.9 A resolution. The unligated enzyme contains four water molecules in the thymidine pocket and reveals a small induced fit on substrate binding. The structure of the ligated enzyme shows for the first time a bound adenine analogue after numerous complexes with thymine and guanine analogues have been reported. The adenine analogue constitutes a new lead compound for enzyme-prodrug gene therapy. In addition, the structure of mutant Q125N modifying the binding site of the natural substrate thymidine in complex with this substrate has been established at 2.5 A resolution. It reveals that neither the binding mode of thymidine nor the polypeptide backbone conformation is altered, except that the two major hydrogen bonds to thymidine are replaced by a single water-mediated hydrogen bond, which improves the relative acceptance of the prodrugs aciclovir and ganciclovir compared with the natural substrate. Accordingly, the mutant structure represents a first step toward improving the virus-directed enzyme-prodrug gene therapy by enzyme engineering.

About this StructureAbout this Structure

1E2I is a Single protein structure of sequence from Human herpesvirus 1. Full crystallographic information is available from OCA.

ReferenceReference

Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography., Vogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, Folkers G, Scapozza L, Schulz GE, Proteins. 2000 Dec 1;41(4):545-53. PMID:11056041 Page seeded by OCA on Fri May 2 14:34:44 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1e2i.gif|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_1e2i", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=APS:9-HYDROXYPROPYLADENINE,+S-ISOMER'>APS</scene>, <scene name='pdbligand=ARP:9-HYDROXYPROPYLADENINE,+R-ISOMER'>ARP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e2i OCA], [http://www.ebi.ac.uk/pdbsum/1e2i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e2i RCSB]</span>
-}}
 '''THE NUCLEOSIDE BINDING SITE OF HERPES SIMPLEX TYPE 1 THYMIDINE KINASE ANALYZED BY X-RAY CRYSTALLOGRAPHY'''
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 [[Category: Schulz, G E.]]
 [[Category: Vogt, J.]]
-[[Category: adenine analog]]
+[[Category: Adenine analog]]
-[[Category: enzyme-prodrug gene therapy]]
+[[Category: Enzyme-prodrug gene therapy]]
-[[Category: nucleoside-binding]]
+[[Category: Nucleoside-binding]]
-[[Category: thymidine kinase]]
+[[Category: Thymidine kinase]]
-[[Category: x-ray crystallography]]
+[[Category: X-ray crystallography]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:34:44 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:53:39 2008''