5jdw
From Proteopedia
(New page: 200px<br /> <applet load="5jdw" size="450" color="white" frame="true" align="right" spinBox="true" caption="5jdw, resolution 2.6Å" /> '''CRYSTAL STRUCTURE OF...) |
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caption="5jdw, resolution 2.6Å" /> | caption="5jdw, resolution 2.6Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN L-ARGININE:GLYCINE AMIDINOTRANSFERASE IN COMPLEX WITH GLYCINE'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN L-ARGININE:GLYCINE AMIDINOTRANSFERASE IN COMPLEX WITH GLYCINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human L-arginine:glycine amidinotransferase (AT) shows large structural | + | Human L-arginine:glycine amidinotransferase (AT) shows large structural changes of the 300-flap and of helix H9 upon binding of L-arginine and L-ornithine, described as a closed and an open conformation (Humm, A., Fritsche, E., Steinbacher, S., and Huber, R. (1997) EMBO J. 16, 3373-3385). To elucidate the structural basis of these induced-fit movements, the x-ray structures of AT in complex with the amidino acceptor glycine and its analogs gamma-aminobutyric acid and delta-aminovaleric acid, as well as in complex with the amidino donor analogs L-alanine, L-alpha-aminobutyric acid, and L-norvaline, have been solved at 2.6-, 2.5-, 2.37-, 2.3-, 2.5-, and 2.4-A resolutions, respectively. The latter three compounds were found to stabilize the open conformer. The glycine analogs bind in a distinct manner and do not induce the transition to the open state. The complex with glycine revealed a third binding mode, reflecting the rather broad substrate specificity of AT. These findings identified a role for the alpha-amino group of the ligand in stabilizing the open conformer. The kinetic, structural, and thermodynamic properties of the mutants ATDeltaM302 and ATDelta11 (lacks 11 residues of H9) confirmed the key role of Asn300 and suggest that in mammalian amidinotransferases, the role of helix H9 is in accelerating amidino transfer by an induced-fit mechanism. Helix H9 does not add to the stability of the protein. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 5JDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLY as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycine_amidinotransferase Glycine amidinotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.4.1 2.1.4.1] Full crystallographic information is available from [http:// | + | 5JDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GLY:'>GLY</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycine_amidinotransferase Glycine amidinotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.4.1 2.1.4.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JDW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:29 2008'' |
Revision as of 17:15, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN L-ARGININE:GLYCINE AMIDINOTRANSFERASE IN COMPLEX WITH GLYCINE
Contents |
Overview
Human L-arginine:glycine amidinotransferase (AT) shows large structural changes of the 300-flap and of helix H9 upon binding of L-arginine and L-ornithine, described as a closed and an open conformation (Humm, A., Fritsche, E., Steinbacher, S., and Huber, R. (1997) EMBO J. 16, 3373-3385). To elucidate the structural basis of these induced-fit movements, the x-ray structures of AT in complex with the amidino acceptor glycine and its analogs gamma-aminobutyric acid and delta-aminovaleric acid, as well as in complex with the amidino donor analogs L-alanine, L-alpha-aminobutyric acid, and L-norvaline, have been solved at 2.6-, 2.5-, 2.37-, 2.3-, 2.5-, and 2.4-A resolutions, respectively. The latter three compounds were found to stabilize the open conformer. The glycine analogs bind in a distinct manner and do not induce the transition to the open state. The complex with glycine revealed a third binding mode, reflecting the rather broad substrate specificity of AT. These findings identified a role for the alpha-amino group of the ligand in stabilizing the open conformer. The kinetic, structural, and thermodynamic properties of the mutants ATDeltaM302 and ATDelta11 (lacks 11 residues of H9) confirmed the key role of Asn300 and suggest that in mammalian amidinotransferases, the role of helix H9 is in accelerating amidino transfer by an induced-fit mechanism. Helix H9 does not add to the stability of the protein.
Disease
Known diseases associated with this structure: AGAT deficiency OMIM:[602360]
About this Structure
5JDW is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Glycine amidinotransferase, with EC number 2.1.4.1 Full crystallographic information is available from OCA.
Reference
The ligand-induced structural changes of human L-Arginine:Glycine amidinotransferase. A mutational and crystallographic study., Fritsche E, Humm A, Huber R, J Biol Chem. 1999 Jan 29;274(5):3026-32. PMID:9915841
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