1hfw: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1hfw.gif|left|200px]]<br /> | [[Image:1hfw.gif|left|200px]]<br /><applet load="1hfw" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1hfw" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1hfw, resolution 1.80Å" /> | caption="1hfw, resolution 1.80Å" /> | ||
'''X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND L-GLUTAMATE'''<br /> | '''X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND L-GLUTAMATE'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
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] | 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] Known structural/functional Sites: <scene name='pdbsite=AS1:Active Site Chain A, TYR-A29 Not Visible In Electron Density'>AS1</scene>, <scene name='pdbsite=AS2:Active Site Chain B, TYR-B29 Not Visible In Electron Density'>AS2</scene>, <scene name='pdbsite=AS3:Active Site Chain C, TYR-C29 Not Visible In Electron Density'>AS3</scene>, <scene name='pdbsite=AS4:Active Site Chain D, TYR-D29 Not Visible In Electron Density'>AS4</scene>, <scene name='pdbsite=LI1:GLU Binding Site For Chain A'>LI1</scene>, <scene name='pdbsite=LI2:GLU Binding Site For Chain B'>LI2</scene>, <scene name='pdbsite=LI3:GLU Binding Site For Chain C'>LI3</scene> and <scene name='pdbsite=LI4:GLU Binding Site For Chain D'>LI4</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HFW OCA]. | ||
==Reference== | ==Reference== | ||
| Line 26: | Line 25: | ||
[[Category: x-ray]] | [[Category: x-ray]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 16:21:25 2007'' | ||
Revision as of 17:11, 18 December 2007
|
X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND L-GLUTAMATE
OverviewOverview
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 StructureAbout this Structure
1HFW is a Single protein structure of sequence from Erwinia chrysanthemi with GLU as ligand. Active as Asparaginase, with EC number 3.5.1.1 Known structural/functional Sites: , , , , , , and . Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Tue Dec 18 16:21:25 2007