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| {{STRUCTURE_1hfw| PDB=1hfw | SCENE= }} | | {{STRUCTURE_1hfw| PDB=1hfw | SCENE= }} |
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| '''X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND L-GLUTAMATE'''
| | ===X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND L-GLUTAMATE=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11341830}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11341830 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11341830}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Structure]] | | [[Category: Structure]] |
| [[Category: X-ray]] | | [[Category: X-ray]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:48:32 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:08:10 2008'' |