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1e2l

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Revision as of 07:55, 13 December 2017

Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine

Structural highlights

1e2l is a 2 chain structure with sequence from Hhv-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1kim, 1vtk, 2vtk, 3vtk, 1ki2, 1ki4, 1ki5, 1ki6, 1ki7, 1ki8, 1e2i, 1e2j, 1e2k, 1e2h, 1e2m, 1e2n, 1e2p
Activity:	Thymidine kinase, with EC number 2.7.1.21
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KITH_HHV11] In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Kinetic and crystallographic analyses of wild-type Herpes simplex virus type 1 thymidine kinase (TK(HSV1)) and its Y101F-mutant [TK(HSV1)(Y101F)] acting on the potent antiviral drug 2'-exo-methanocarba-thymidine (MCT) have been performed. The kinetic study reveals a 12-fold K(M) increase for thymidine processed with Y101F as compared to the wild-type TK(HSV1). Furthermore, MCT is a substrate for both wild-type and mutant TK(HSV1). Its binding affinity for TK(HSV1) and TK(HSV1)(Y101F), expressed as K(i), is 11 microM and 51 microM, respectively, whereas the K(i) for human cytosolic thymidine kinase is as high as 1.6 mM, rendering TK(HSV1) a selectivity filter for antiviral activity. Moreover, TK(HSV1)(Y101F) shows a decrease in the quotient of the catalytic efficiency (k(cat)/K(M)) of dT over MCT corresponding to an increased specificity for MCT when compared to the wild-type enzyme. Crystal structures of wild-type and mutant TK(HSV1) in complex with MCT have been determined to resolutions of 1.7 and 2.4 A, respectively. The thymine moiety of MCT binds like the base of dT while the conformationally restricted bicyclo[3.1.0]hexane, mimicking the sugar moiety, assumes a 2'-exo envelope conformation that is flatter than the one observed for the free compound. The hydrogen bond pattern around the sugar-like moiety differs from that of thymidine, revealing the importance of the rigid conformation of MCT with respect to hydrogen bonds. These findings make MCT a lead compound in the design of resistance-repellent drugs for antiviral therapy, and mutant Y101F, in combination with MCT, opens new possibilities for gene therapy.

Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine.,Prota A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G, Scapozza L Biochemistry. 2000 Aug 8;39(31):9597-603. PMID:10924157^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Prota A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G, Scapozza L. Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine. Biochemistry. 2000 Aug 8;39(31):9597-603. PMID:10924157

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1e2l"

@@ Line 1: / Line 1: @@
-==KINETICS AND CRYSTAL STRUCTURE OF THE WILD-TYPE AND THE ENGINEERED Y101F MUTANT OF HERPES SIMPLEX VIRUS TYPE 1 THYMIDINE KINASE INTERACTING WITH (NORTH)-METHANOCARBA-THYMIDINE==
+==Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine==
 <StructureSection load='1e2l' size='340' side='right' caption='[[1e2l]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kim|1kim]], [[1vtk|1vtk]], [[2vtk|2vtk]], [[3vtk|3vtk]], [[1ki2|1ki2]], [[1ki4|1ki4]], [[1ki5|1ki5]], [[1ki6|1ki6]], [[1ki7|1ki7]], [[1ki8|1ki8]], [[1e2i|1e2i]], [[1e2j|1e2j]], [[1e2k|1e2k]], [[1e2h|1e2h]], [[1e2m|1e2m]], [[1e2n|1e2n]], [[1e2p|1e2p]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e2l OCA], [http://pdbe.org/1e2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e2l RCSB], [http://www.ebi.ac.uk/pdbsum/1e2l PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e2l OCA], [http://pdbe.org/1e2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e2l RCSB], [http://www.ebi.ac.uk/pdbsum/1e2l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1e2l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e2/1e2l_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e2/1e2l_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 1e2l" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Thymidine kinase|Thymidine kinase]]
 == References ==
 <references/>

1e2l

From Proteopedia

Revision as of 07:55, 13 December 2017

Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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