2gcq
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(New page: 200px<br /><applet load="2gcq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gcq, resolution 2.0Å" /> '''Fully ligated E.Coli ...)
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Revision as of 09:00, 21 November 2007
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Fully ligated E.Coli Adenylosuccinate Synthetase with GTP, 2'-deoxy-IMP and Hadacidin
Overview
Adenylosuccinate synthetase catalyzes the first committed step in the de, novo biosynthesis of AMP, coupling L-aspartate and IMP to form, adenylosuccinate. Km values of IMP and 2'-deoxy-IMP are nearly identical, with each substrate supporting comparable maximal velocities. Nonetheless, the Km value for L-aspartate and the Ki value for hadacidin (a competitive, inhibitor with respect to L-aspartate) are 29-57-fold lower in the, presence of IMP than in the presence of 2'-deoxy-IMP. Crystal structures, of the synthetase ligated with hadacidin, GDP, and either 6-phosphoryl-IMP, or 2'-deoxy-6-phosphoryl-IMP are identical except for the presence of a, cavity normally occupied by the 2'-hydroxyl group of IMP. In the presence, of 6-phosphoryl-IMP and GDP (hadacidin absent), the L-aspartate pocket can, retain its fully ligated conformation, forming hydrogen bonds between the, 2'-hydroxyl group of IMP and sequence-invariant residues. In the presence, of 2'-deoxy-6-phosphoryl-IMP and GDP, however, the L-aspartate pocket is, poorly ordered. The absence of the 2'-hydroxyl group of the, deoxyribonucleotide may destabilize binding of the ligand to the, L-aspartate pocket by disrupting hydrogen bonds that maintain a favorable, protein conformation and by the introduction of a cavity into the fully, ligated active site. At an approximate energy cost of 2.2 kcal/mol, the, unfavorable thermodynamics of cavity formation may be the major factor in, destabilizing ligands at the L-aspartate pocket.
About this Structure
2GCQ is a Single protein structure of sequence from Escherichia coli with MG, DOI, GDP and HAD as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
Reference
Cavitation as a mechanism of substrate discrimination by adenylosuccinate synthetases., Iancu CV, Zhou Y, Borza T, Fromm HJ, Honzatko RB, Biochemistry. 2006 Sep 26;45(38):11703-11. PMID:16981730
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