1lvg
From Proteopedia
(New page: 200px<br /><applet load="1lvg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lvg, resolution 2.1Å" /> '''Crystal structure of ...) |
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| - | [[Image:1lvg.gif|left|200px]]<br /><applet load="1lvg" size=" | + | [[Image:1lvg.gif|left|200px]]<br /><applet load="1lvg" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1lvg, resolution 2.1Å" /> | caption="1lvg, resolution 2.1Å" /> | ||
'''Crystal structure of mouse guanylate kinase in complex with GMP and ADP'''<br /> | '''Crystal structure of mouse guanylate kinase in complex with GMP and ADP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1LVG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with K, ADP and 5GP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Guanylate_kinase Guanylate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.8 2.7.4.8] Full crystallographic information is available from [http:// | + | 1LVG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=5GP:'>5GP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Guanylate_kinase Guanylate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.8 2.7.4.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LVG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
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Revision as of 11:48, 21 February 2008
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Crystal structure of mouse guanylate kinase in complex with GMP and ADP
Overview
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.
About this Structure
1LVG is a Single protein structure of sequence from Mus musculus with , and as ligands. Active as Guanylate kinase, with EC number 2.7.4.8 Full crystallographic information is available from OCA.
Reference
Structural characterization of the closed conformation of mouse guanylate kinase., Sekulic N, Shuvalova L, Spangenberg O, Konrad M, Lavie A, J Biol Chem. 2002 Aug 16;277(33):30236-43. Epub 2002 May 29. PMID:12036965
Page seeded by OCA on Thu Feb 21 13:48:50 2008
Categories: Guanylate kinase | Mus musculus | Single protein | Konrad, M. | Lavie, A. | Sekulic, N. | Shuvalova, L. | Spangenberg, O. | 5GP | ADP | K | Gmp kinase | Transferase
