1kp2
From Proteopedia
(New page: 200px<br /><applet load="1kp2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kp2, resolution 2.00Å" /> '''Crystal Structure of...) |
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| - | [[Image:1kp2.jpg|left|200px]]<br /><applet load="1kp2" size=" | + | [[Image:1kp2.jpg|left|200px]]<br /><applet load="1kp2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kp2, resolution 2.00Å" /> | caption="1kp2, resolution 2.00Å" /> | ||
'''Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP'''<br /> | '''Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Argininosuccinate synthetase (AS) is the rate-limiting enzyme of both the | + | Argininosuccinate synthetase (AS) is the rate-limiting enzyme of both the urea and arginine-citrulline cycles. In mammals, deficiency of AS leads to citrullinemia, a debilitating and often fatal autosomal recessive urea cycle disorder, whereas its overexpression for sustained nitric oxide production via the arginine-citrulline cycle leads to the potentially fatal hypotension associated with septic and cytokine-induced circulatory shock. The crystal structures of Escherichia coli argininosuccinate synthetase (EAS) in complex with ATP and with ATP and citrulline have been determined at 2.0-A resolution. These are the first EAS structures to be solved in the presence of a nucleotide substrate and clearly identify the residues that interact with both ATP and citrulline. Two distinct conformations are revealed for ATP, both of which are believed to be catalytically relevant. In addition, comparisons of these EAS structures with those of the apoenzyme and EAS complexed with aspartate and citrulline (Lemke, C. T., and Howell, P. L. (2001) Structure (Lond.) 9, 1153-1164) provide structural evidence of ATP-induced conformational changes in the nucleotide binding domain. Combined, these structures also provide structural explanations of some of the observed kinetic properties of the enzyme and have enabled a detailed enzymatic mechanism of AS catalysis to be proposed. |
==About this Structure== | ==About this Structure== | ||
| - | 1KP2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4, ATP and GAI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Argininosuccinate_synthase Argininosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.5 6.3.4.5] Full crystallographic information is available from [http:// | + | 1KP2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=GAI:'>GAI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Argininosuccinate_synthase Argininosuccinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.5 6.3.4.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KP2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Howell, P | + | [[Category: Howell, P L.]] |
| - | [[Category: Lemke, C | + | [[Category: Lemke, C T.]] |
[[Category: ATP]] | [[Category: ATP]] | ||
[[Category: GAI]] | [[Category: GAI]] | ||
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[[Category: n-type atp pyrophosphatase]] | [[Category: n-type atp pyrophosphatase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:36:28 2008'' |
Revision as of 11:36, 21 February 2008
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Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP
Overview
Argininosuccinate synthetase (AS) is the rate-limiting enzyme of both the urea and arginine-citrulline cycles. In mammals, deficiency of AS leads to citrullinemia, a debilitating and often fatal autosomal recessive urea cycle disorder, whereas its overexpression for sustained nitric oxide production via the arginine-citrulline cycle leads to the potentially fatal hypotension associated with septic and cytokine-induced circulatory shock. The crystal structures of Escherichia coli argininosuccinate synthetase (EAS) in complex with ATP and with ATP and citrulline have been determined at 2.0-A resolution. These are the first EAS structures to be solved in the presence of a nucleotide substrate and clearly identify the residues that interact with both ATP and citrulline. Two distinct conformations are revealed for ATP, both of which are believed to be catalytically relevant. In addition, comparisons of these EAS structures with those of the apoenzyme and EAS complexed with aspartate and citrulline (Lemke, C. T., and Howell, P. L. (2001) Structure (Lond.) 9, 1153-1164) provide structural evidence of ATP-induced conformational changes in the nucleotide binding domain. Combined, these structures also provide structural explanations of some of the observed kinetic properties of the enzyme and have enabled a detailed enzymatic mechanism of AS catalysis to be proposed.
About this Structure
1KP2 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Argininosuccinate synthase, with EC number 6.3.4.5 Full crystallographic information is available from OCA.
Reference
Substrate induced conformational changes in argininosuccinate synthetase., Lemke CT, Howell PL, J Biol Chem. 2002 Apr 12;277(15):13074-81. Epub 2002 Jan 23. PMID:11809762
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