1hfw: Difference between revisions

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.

1HFW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Erwinia_chrysanthemi Erwinia chrysanthemi] with GLU as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Asparaginase Asparaginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.1 3.5.1.1] Structure known Active Sites: AS1, AS2, AS3, AS4, LI1, LI2, LI3 and LI4. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HFW OCA].  

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