1hg1

X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND D-ASPARTATEX-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND D-ASPARTATE

Structural highlights 1hg1 is a 4 chain structure with sequence from Erwinia chrysanthemi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1hfj, 1hfk, 1hfw, 1hg0 Activity: Asparaginase, with EC number 3.5.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Other substrates of asparaginases include L-glutamine, D-asparagine, and succinic acid monoamide. In this report, we present high-resolution crystal structures of the complexes of Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions that also can serve as substrates, namely L-glutamic acid (L-Glu), D-aspartic acid (D-Asp), and succinic acid (Suc). Comparison of the four independent active sites within each complex indicates unique and specific binding of the ligand molecules; the mode of binding is also similar between complexes. The lack of the alpha-NH3(+) group in Suc, compared to L-Asp, does not affect the binding mode. The side chain of L-Glu, larger than that of L-Asp, causes several structural distortions in the ErA active side. The active site flexible loop (residues 15-33) does not exhibit stable conformation, resulting in suboptimal orientation of the nucleophile, Thr15. Additionally, the delta-COO(-) plane of L-Glu is approximately perpendicular to the plane of gamma-COO(-) in L-Asp bound to the asparaginase active site. Binding of D-Asp to the ErA active site is very distinctive compared to the other ligands, suggesting that the low activity of ErA against D-Asp could be mainly attributed to the low k(cat) value. A comparison of the amino acid sequence and the crystal structure of ErA with those of other bacterial L-asparaginases shows that the presence of two active-site residues, Glu63(ErA) and Ser254(ErA), may correlate with significant glutaminase activity, while their substitution by Gln and Asn, respectively, may lead to minimal L-glutaminase activity. Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase.,Aghaiypour K, Wlodawer A, Lubkowski J Biochemistry. 2001 May 15;40(19):5655-64. PMID:11341830 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Asparaginase

spinqualitylabelsall models 1hg1, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image