| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print May 29, 2002
Biochemistry and Molecular Biology, University of Illinois at Chicago, Chicago, IL 60607
Corresponding Author: lavie{at}uic.edu
Guanylate kinase (GMPK) is nucleoside monophosphate kinase that catalyses the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. In addition to phosphorylating GMP, antiviral prodrugs such as acyclovir, ganciclovir and carbovir, and anticancer prodrugs such as the thiopurines, are dependant on GMPK for their activation. Hence, structural information on mammalian GMPK could play a role in the design of improved antiviral and antineoplastic agents. Here we present the structure of the mouse enzyme in an abortive complex with the nucleotides ADP and GMP, refined at 2.1 Å resolution with a final crystallographic R-factor of 0.20 (Rfree = 0.24). Guanylate kinase is a member of the nucleoside monophosphate (NMP)-kinase family, a family of enzymes that despite having a low primary structure identity share a similar fold, which consists of 3 structurally distinct regions termed CORE, LID and NMP-binding. Previous studies on the yeast enzyme have shown that these parts move as rigid bodies upon substrate binding. It has been proposed that consecutive binding of substrates leads to "closing" of the active site bringing the NMP-binding and LID regions closer to each other and to CORE. Our structure, which is the first of any guanylate kinase with both substrates bound, supports this hypothesis. It also reveals the binding site of ATP, and implicates arginines 44, 137, and 148 (in addition to the invariant P-loop lysine) as candidates for catalyzing the chemical step of the phosphoryl transfer.
J. Biol. Chem, 10.1074/jbc.M204668200
Submitted on May 13, 2002
Revised on May 29, 2002
Accepted on May 29, 2002
Structural characterization of the closed conformation of mouse guanylate kinase
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Stanley, S. Krueger, V. A. Parsegian, and D. C. Rau Protein Structure and Hydration Probed by SANS and Osmotic Stress Biophys. J., April 1, 2008; 94(7): 2777 - 2789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sekulic, M. Konrad, and A. Lavie Structural Mechanism for Substrate Inhibition of the Adenosine 5'-Phosphosulfate Kinase Domain of Human 3'-Phosphoadenosine 5'-Phosphosulfate Synthetase 1 and Its Ramifications for Enzyme Regulation J. Biol. Chem., July 27, 2007; 282(30): 22112 - 22121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Choi and G. Zocchi Guanylate Kinase, Induced Fit, and the Allosteric Spring Probe Biophys. J., March 1, 2007; 92(5): 1651 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kotaka, B. Dhaliwal, J. Ren, C. E. Nichols, R. Angell, M. Lockyer, A. R. Hawkins, and D. K. Stammers Structures of S. aureus thymidylate kinase reveal an atypical active site configuration and an intermediate conformational state upon substrate binding Protein Sci., April 1, 2006; 15(4): 774 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Segura-Pena, N. Sekulic, S. Ort, M. Konrad, and A. Lavie Substrate-induced Conformational Changes in Human UMP/CMP Kinase J. Biol. Chem., August 6, 2004; 279(32): 33882 - 33889. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
