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4uxh

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Revision as of 01:57, 10 March 2017

Leishmania major Thymidine Kinase in complex with AP5dT

Structural highlights

4uxh is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4uxi, 4uxj
Activity:	Thymidine kinase, with EC number 2.7.1.21
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Leishmania spp. is a protozoan parasite and the causative agent of leishmaniasis. Thymidine kinase (TK) catalyses the transfer of the gamma-phosphate of ATP to 2'-deoxythymidine (dThd) forming thymidine monophosphate (dTMP). L. major Type II TK (LmTK) has been previously shown to be important for infectivity of the parasite and therefore has potential as a drug target for anti-leishmanial therapy. In this study, we determined the enzymatic properties and the 3D structures of holo forms of the enzyme. LmTK efficiently phosphorylates dThd and dUrd and has high structural homology to TKs from other species. However, it significantly differs in its kinetic properties from Trypanosoma brucei TK since purines are not substrates of the enzyme and dNTPs such as dUTP inhibit LmTK. The enzyme had Km and kcat values for dThd of 1.1 muM and 2.62 s-1 and exhibits cooperative binding for ATP. Additionally, we show that the anti-retroviral prodrug zidovudine (3-azido-3-deoxythymidine, AZT) and 5'-modified dUrd can be readily phosphorylated by LmTK. The production of recombinant enzyme at a level suitable for structural studies was achieved by the construction of C-terminal truncated versions of the enzyme and the use of a baculoviral expression system. The structures of the catalytic core of LmTK in complex with dThd, the negative feedback regulator dTTP and the bi-substrate analogue AP5dT, were determined to 2.74, 3.00 and 2.40 A, respectively, and provide the structural basis for exclusion of purines and dNTP inhibition. The results will aid the process of rational drug design with LmTK as a potential target for anti-leishmanial drugs.

Structural and Kinetic Characterization of Thymidine Kinase from Leishmania major.,Timm J, Bosch-Navarrete C, Recio E, Nettleship JE, Rada H, Gonzalez-Pacanowska D, Wilson KS PLoS Negl Trop Dis. 2015 May 15;9(5):e0003781. doi: 10.1371/journal.pntd.0003781., eCollection 2015 May. PMID:25978379^[1]

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

References

↑ Timm J, Bosch-Navarrete C, Recio E, Nettleship JE, Rada H, Gonzalez-Pacanowska D, Wilson KS. Structural and Kinetic Characterization of Thymidine Kinase from Leishmania major. PLoS Negl Trop Dis. 2015 May 15;9(5):e0003781. doi: 10.1371/journal.pntd.0003781., eCollection 2015 May. PMID:25978379 doi:http://dx.doi.org/10.1371/journal.pntd.0003781

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4uxh"

@@ Line 1: / Line 1: @@
 ==Leishmania major Thymidine Kinase in complex with AP5dT==
 <StructureSection load='4uxh' size='340' side='right' caption='[[4uxh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uxi|4uxi]], [[4uxj|4uxj]]</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=4uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uxh RCSB], [http://www.ebi.ac.uk/pdbsum/4uxh 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=4uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uxh OCA], [http://pdbe.org/4uxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uxh RCSB], [http://www.ebi.ac.uk/pdbsum/4uxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uxh ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4uxh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Thymidine kinase|Thymidine kinase]]
 == References ==
 <references/>

4uxh

From Proteopedia

Revision as of 01:57, 10 March 2017

Leishmania major Thymidine Kinase in complex with AP5dT

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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