1kp3: Difference between revisions

Revision as of 23:00, 2 May 2008

Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP and Citrulline

OverviewOverview

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 StructureAbout this Structure

1KP3 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 23:00:07 2008

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OCA

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 [[Image:1kp3.jpg|left|200px]]
- {{Structure
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-|ACTIVITY= <span class='plainlinks'>[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] </span>
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-|RELATEDENTRY=[[1k92|1K92]], [[1k97|1K97]], [[1kp2|1KP2]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kp3 OCA], [http://www.ebi.ac.uk/pdbsum/1kp3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kp3 RCSB]</span>
-}}
 '''Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP and Citrulline'''
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 [[Category: Howell, P L.]]
 [[Category: Lemke, C T.]]
-[[Category: n-type atp pyrophosphatase]]
+[[Category: N-type atp pyrophosphatase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 23:00:07 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:51:35 2008''