1LVG

Crystal structure of mouse guanylate kinase in complex with GMP and ADP

1LVG の概要

• エントリーDOI: 10.2210/pdb1lvg/pdb
• 分子名称: Guanylate kinase, POTASSIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: transferase, gmp kinase, guanylate kinase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22777.46

構造登録者

Sekulic, N.,Shuvalova, L.,Spangenberg, O.,Konrad, M.,Lavie, A. (登録日: 2002-05-28, 公開日: 2002-12-11, 最終更新日: 2024-02-14)

主引用文献

Sekulic, N.,Shuvalova, L.,Spangenberg, O.,Konrad, M.,Lavie, A.
Structural characterization of the closed conformation of mouse guanylate kinase.
J.Biol.Chem., 277:30236-30243, 2002

PubMed Abstract: 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 A 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.

PubMed: 12036965
DOI: 10.1074/jbc.M204668200

実験手法

X-RAY DIFFRACTION (2.1 Å)