Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Display Documents



  history
ID: 16636.0, MPI für biophysikalische Chemie / Ehemalige Abteilungen
Structural characterization of the closed conformation of mouse guanylate kinase
Authors:Sekulic, N.; Shuvalova, L.; Spangenberg, O.; Konrad, M.; Lavie, A.
Language:English
Date of Publication (YYYY-MM-DD):2002-08-16
Title of Journal:Journal of Biological Chemistry
Volume:277
Issue / Number:33
Start Page:30236
End Page:30243
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that catalyzes 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 dependent 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 Angstrom resolution with a final crystallographic R factor of 0.19 (R-free = 0.23). 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 three structurally distinct regions termed the CORE, LID, and NMP-binding regions. 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 the CORE region. 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.
Comment of the Author/Creator:Date: 2002, AUG 16
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Dieter Gallwitz / 150
MPI für biophysikalische Chemie/AG Manfred Konrad
External Affiliations:Univ Illinois, Dept Biochem & Mol Biol, 1819 W Polk St,; Chicago, IL 60612 USA
Identifiers:URL:http://www.jbc.org/content/277/33/30236.full.pdf+h...
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.