2gcq | pdb_00002gcq

Fully ligated E.Coli Adenylosuccinate Synthetase with GTP, 2'-deoxy-IMP and Hadacidin

spinqualitylabelsall models 2gcq, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2gcq is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DOI, GDP, HDA, MG Gene: purA, adeK (Escherichia coli) Activity: Adenylosuccinate synthase, with EC number 6.3.4.4 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PURA_ECOLI] Plays an important role in the de novo pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP (By similarity).[HAMAP-Rule:MF_00011] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adenylosuccinate Synthetase

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