alexa Inhibition of adenosine and thymidylate kinases by bisubstrate analogs.
Biochemistry

Biochemistry

Biochemistry & Physiology: Open Access

Author(s): Bone R, Cheng YC, Wolfenden R

Abstract Share this page

Abstract Potential bisubstrate analogs, in which the 5'-hydroxyl group of adenosine was joined to the phosphoryl group acceptor by polyphosphoryl bridges of varying length (ApnX, where n is the number of phosphoryl groups and X is the nucleoside moiety of the acceptor), were tested as inhibitors of human liver adenosine kinase and of thymidylate kinase from peripheral blast cells of patients with acute myelocytic leukemia. Adenosine kinase was most strongly inhibited by P1,P4-(diadenosine 5')-tetraphosphate (Kd = 30 nM) and P1,P5-(diadenosine 5')-pentaphosphate (Kd = 73 nM). Thymidylate kinase was most strongly inhibited by P1-(adenosine 5')-P5-(thymidine 5')-pentaphosphate (Kd = 120 nM) and by P1(adenosine 5')-P6-(thymidine 5')-hexaphosphate (Kd = 43 nM). In these enzymes, as in adenylate and thymidylate kinases, strongest inhibition was achieved in compounds containing one or two more phosphoryl groups than the substrates combined. These results support the view that nucleoside and nucleotide kinases mediate direct transfer of phosphoryl groups from ATP to acceptors, rather than acting by a double displacement mechanism.
This article was published in J Biol Chem and referenced in Biochemistry & Physiology: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference on Structural Biology
    September 18-20, 2017 Zurich, Switzerland

  •  2nd International Conference on Biochemistry
    Sep 21-22, 2017, Macau, Hong Kong
  • 2nd International Conference on Biochemistry
    September 28-29, 2017 Dubai, UAE

  • 3rd Annual Congress on Bioscience
    October 16-17, 2017 Dubai,UAE

  • 3rd International Conference on Transcriptomics
    October 30 - November 01, 2017 Bangkok, Thailand

  • 3rd International Conference on Genetic and Protein Engineering (10 Plenary Forums - 1 Event)
    November 08-09, 2017 Las Vegas, USA

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords