A novel viral thymidylate kinase with dual kinase activity

Journal of Bioenergetics and Biomembranes
Eduardo Guevara-HernandezRogerio R Sotelo-Mundo

Abstract

Nucleotide phosphorylation is a key step in DNA replication and viral infections, since suitable levels of nucleotide triphosphates pool are required for this process. Deoxythymidine monophosphate (dTMP) is produced either by de novo or salvage pathways, which is further phosphorylated to deoxythymidine triphosphate (dTTP). Thymidyne monophosphate kinase (TMK) is the enzyme in the junction of both pathways, which phosphorylates dTMP to yield deoxythymidine diphosphate (dTDP) using adenosine triphosphate (ATP) as a phosphate donor. White spot syndrome virus (WSSV) genome contains an open reading frame (ORF454) that encodes a thymidine kinase and TMK domains in a single polypeptide. We overexpressed the TMK ORF454 domain (TMKwssv) and its specific activity was measured with dTMP and dTDP as phosphate acceptors. We found that TMKwssv can phosphorylate dTMP to yield dTDP and also is able to use dTDP as a substrate to produce dTTP. Kinetic parameters K M and k cat were calculated for dTMP (110 μM, 3.6 s(-1)), dTDP (251 μM, 0.9 s(-1)) and ATP (92 μM, 3.2 s(-1)) substrates, and TMKwssv showed a sequential ordered bi-bi reaction mechanism. The binding constants K d for dTMP (1.9 μM) and dTDP (10 μM) to TMKwssv were determined by Isothe...Continue Reading

References

Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·A LavieI Schlichting
Sep 24, 1999·Occupational and Environmental Medicine·D BarisS Wacholder
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G G YegutkinS Jalkanen
May 23, 2001·Protein Science : a Publication of the Protein Society·H Munier-LehmannG Labesse
Jul 13, 2001·Virology·M C van HultenJ M Vlak
Jul 27, 2001·Journal of Molecular Biology·I Li de la SierraM Delarue
May 12, 2004·Mini Reviews in Medicinal Chemistry·Arnon Lavie, Manfred Konrad
Dec 13, 2005·The FEBS Journal·Dimitri TopalisDominique Deville-Bonne
Aug 16, 2008·Drug Discovery Today·Ernesto Freire
Oct 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christophe CaillatPhilippe Meyer
Jun 30, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Aldo A Arvizu-FloresRogerio R Sotelo-Mundo
Jan 8, 2011·Biological & Pharmaceutical Bulletin·Mahmoud Kandeel, Yukio Kitade
Jan 14, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Enrique de-la-Re-VegaRogerio R Sotelo-Mundo
Aug 16, 2011·Drug Discovery Today·Yuko Kawasaki, Ernesto Freire
Apr 25, 2012·Journal of Bioenergetics and Biomembranes·Idania E Quintero-ReyesRogerio R Sotelo-Mundo
Sep 4, 2013·Journal of Biomolecular Structure & Dynamics·Ana Paula GuimarãesTanos Celmar Costa França
Feb 22, 2014·Acta Tropica·Pawan Kumar DohareyJitendra Kumar Saxena
Aug 26, 2014·Genome Announcements·Abdelbaset I YagubiAntonet M Svircev
Sep 10, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Alonso A López-ZavalaRogerio R Sotelo-Mundo

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Respiration

This feed focuses on cellular respiration in bacteria, known as bacterial respiration. Discover the latest research here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.