PMID- 26315341
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20220801
IS  - 1573-6881 (Electronic)
IS  - 0145-479X (Linking)
VI  - 47
IP  - 5
DP  - 2015 Oct
TI  - A novel viral thymidylate kinase with dual kinase activity.
PG  - 431-40
LID - 10.1007/s10863-015-9622-z [doi]
AB  - 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 muM, 3.6 s(-1)), dTDP (251 
      muM, 0.9 s(-1)) and ATP (92 muM, 3.2 s(-1)) substrates, and TMKwssv showed a 
      sequential ordered bi-bi reaction mechanism. The binding constants K d for dTMP 
      (1.9 muM) and dTDP (10 muM) to TMKwssv were determined by Isothermal Titration 
      Calorimetry. The affinity of the nucleotidic analog stavudine monophosphate was 
      in the same order of magnitude (K d 3.6 muM) to the canonical substrate dTMP. 
      These results suggest that nucleotide analogues such as stavudine could be a 
      suitable antiviral strategy for the WSSV-associated disease.
FAU - Guevara-Hernandez, Eduardo
AU  - Guevara-Hernandez E
AD  - Centro de Investigacion en Alimentacion y Desarrollo, A.C. (CIAD), Carretera a 
      Ejido La Victoria Km 0.6, Apartado Postal 1735, Hermosillo, Sonora, 83304, 
      Mexico.
AD  - Departamento de Investigacion y Posgrado en Alimentos, Universidad de Sonora, 
      Blvd. Rosales y Luis Encinas, Hermosillo, Sonora, 83000, Mexico.
FAU - Arvizu-Flores, Aldo A
AU  - Arvizu-Flores AA
AD  - Departamento de Ciencias Quimico Biologicas, Universidad de Sonora, Blvd. Rosales 
      y Luis Encinas, Hermosillo, Sonora, 83000, Mexico. aldoarvizu@guayacan.uson.mx.
FAU - Lugo-Sanchez, Maria E
AU  - Lugo-Sanchez ME
AD  - Centro de Investigacion en Alimentacion y Desarrollo, A.C. (CIAD), Carretera a 
      Ejido La Victoria Km 0.6, Apartado Postal 1735, Hermosillo, Sonora, 83304, 
      Mexico.
FAU - Velazquez-Contreras, Enrique F
AU  - Velazquez-Contreras EF
AD  - Departamento de Ciencias Quimico Biologicas, Universidad de Sonora, Blvd. Rosales 
      y Luis Encinas, Hermosillo, Sonora, 83000, Mexico.
FAU - Castillo-Yanez, Francisco J
AU  - Castillo-Yanez FJ
AD  - Departamento de Ciencias Quimico Biologicas, Universidad de Sonora, Blvd. Rosales 
      y Luis Encinas, Hermosillo, Sonora, 83000, Mexico.
FAU - Brieba, Luis G
AU  - Brieba LG
AD  - Laboratorio Nacional de Genomica para la Biodiversidad (LANGEBIO), Centro de 
      Investigacion y Estudios Avanzados-Unidad Irapuato, Km 9.6 Libramiento Norte 
      Carretera Irapuato-Leon, Apartado Postal 629, Irapuato, Guanajuato, 36500, 
      Mexico.
FAU - Sotelo-Mundo, Rogerio R
AU  - Sotelo-Mundo RR
AD  - Centro de Investigacion en Alimentacion y Desarrollo, A.C. (CIAD), Carretera a 
      Ejido La Victoria Km 0.6, Apartado Postal 1735, Hermosillo, Sonora, 83304, 
      Mexico. rrs@ciad.mx.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150828
PL  - United States
TA  - J Bioenerg Biomembr
JT  - Journal of bioenergetics and biomembranes
JID - 7701859
RN  - 0 (Viral Proteins)
RN  - EC 2.7.4.4 (Nucleoside-Phosphate Kinase)
RN  - EC 2.7.4.9 (dTMP kinase)
SB  - IM
MH  - Nucleoside-Phosphate Kinase/antagonists & inhibitors/*chemistry/genetics
MH  - *Open Reading Frames
MH  - Protein Structure, Tertiary
MH  - Substrate Specificity/physiology
MH  - Viral Proteins/antagonists & inhibitors/*chemistry/genetics
MH  - White spot syndrome virus 1/*enzymology/genetics
OTO - NOTNLM
OT  - Diphosphate kinase
OT  - Isothermal titration calorimetry
OT  - Nucleotide phosphorylation
OT  - Thymidylate kinase
OT  - White spot syndrome virus
EDAT- 2015/09/01 06:00
MHDA- 2016/08/02 06:00
CRDT- 2015/08/29 06:00
PHST- 2015/03/25 00:00 [received]
PHST- 2015/08/17 00:00 [accepted]
PHST- 2015/08/29 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
AID - 10.1007/s10863-015-9622-z [pii]
AID - 10.1007/s10863-015-9622-z [doi]
PST - ppublish
SO  - J Bioenerg Biomembr. 2015 Oct;47(5):431-40. doi: 10.1007/s10863-015-9622-z. Epub 
      2015 Aug 28.