1hg1: Difference between revisions

==Overview==

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.

==About this Structure==

1HG1 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 <scene name='pdbligand=DAS:'>DAS</scene> 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] Known structural/functional Sites: <scene name='pdbsite=AS1:Active+Site+Chain+A,+TYR-29+Not+Visible+I+Electron+Density'>AS1</scene>, <scene name='pdbsite=AS2:Active+Site+Chain+B,+TYR-29+Not+Visible+I+Electron+Density'>AS2</scene>, <scene name='pdbsite=AS3:Active+Site+Chain+C,+TYR-29+Not+Visible+I+Electron+Density'>AS3</scene>, <scene name='pdbsite=AS4:Active+Site+Chain+D,+TYR-29+Not+Visible+I+Electron+Density'>AS4</scene>, <scene name='pdbsite=LI1:Dsp+(D-ASP)+Binding+Site+For+Chain+A'>LI1</scene>, <scene name='pdbsite=LI2:Dsp+(D-ASP)+Binding+Site+For+Chain+B'>LI2</scene>, <scene name='pdbsite=LI3:Dsp+(D-ASP)+Binding+Site+For+Chain+C'>LI3</scene> and <scene name='pdbsite=LI4:Dsp+(D-ASP)+Binding+Site+For+Chain+D'>LI4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HG1 OCA].

 

[[Category: Erwinia chrysanthemi]]

[[Category: Single protein]]

[[Category: Kolyani, K A.]]

[[Category: Lubkowski, J.]]

[[Category: Wlodawer, A.]]