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| [[Image:1hg0.gif|left|200px]]<br />
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| <applet load="1hg0" size="450" color="white" frame="true" align="right" spinBox="true"
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| caption="1hg0, resolution 1.90Å" />
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| '''X-RAY STRUCTURE OF THE COMPLEX BETWEEN ERWINIA CHRYSANTHEMI L-ASPARAGINASE AND SUCCINIC ACID'''<br />
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| ==Overview== | | ==X-ray structure of the complex between Erwinia chrysanthemi L-asparaginase and succinic acid== |
| 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.
| | <StructureSection load='1hg0' size='340' side='right'caption='[[1hg0]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1hg0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Dickeya_chrysanthemi Dickeya chrysanthemi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HG0 FirstGlance]. <br> |
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hg0 OCA], [https://pdbe.org/1hg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hg0 RCSB], [https://www.ebi.ac.uk/pdbsum/1hg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hg0 ProSAT]</span></td></tr> |
| | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/ASPG_DICCH ASPG_DICCH] |
| | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> |
| | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hg/1hg0_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> |
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hg0 ConSurf]. |
| | <div style="clear:both"></div> |
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| ==About this Structure== | | ==See Also== |
| 1HG0 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 SIN 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=1HG0 OCA].
| | *[[Asparaginase 3D structures|Asparaginase 3D structures]] |
| | | __TOC__ |
| ==Reference==
| | </StructureSection> |
| 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11341830 11341830]
| | [[Category: Dickeya chrysanthemi]] |
| [[Category: Asparaginase]]
| | [[Category: Large Structures]] |
| [[Category: Erwinia chrysanthemi]] | | [[Category: Kolyani KA]] |
| [[Category: Single protein]] | | [[Category: Lubkowski J]] |
| [[Category: Kolyani, K.A.]] | | [[Category: Wlodawer A]] |
| [[Category: Lubkowski, J.]] | |
| [[Category: Wlodawer, A.]] | |
| [[Category: SIN]]
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| [[Category: asparaginase]]
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| [[Category: complex]]
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| [[Category: d-aspartate]]
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| [[Category: hydrolase]]
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| [[Category: structure]]
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| [[Category: x-ray]]
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| ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:31:31 2007''
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