View source for 5mq5


==A protease-resistant N24S Escherichia coli Asparaginase mutant with outstanding stability and enhanced anti-leukaemic activity==
<StructureSection load='5mq5' size='340' side='right'caption='[[5mq5]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mq5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MQ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MQ5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ansB, b2957, JW2924 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mq5 OCA], [http://pdbe.org/5mq5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mq5 RCSB], [http://www.ebi.ac.uk/pdbsum/5mq5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mq5 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
L-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics. Herein, we present the biochemical, structural and in vitro antiproliferative characterization of a new EcAII variant, N24S. The mutant shows completely preserved asparaginase and glutaminase activities, long-term storage stability, improved thermal parameters, and outstanding resistance to proteases derived from leukaemia cells. Structural analysis demonstrates a modification in the hydrogen bond network related to residue 24, while Normal Mode-based geometric Simulation and Molecular Dynamics predict a general rigidification of the monomer as compared to wild-type. These improved features render N24S a potential alternative treatment to reduce the number of drug administrations in vivo and to successfully address one of the major current challenges of ALL treatment: spontaneous, protease-dependent and immunological inactivation of ASNase.

A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro.,Maggi M, Mittelman SD, Parmentier JH, Colombo G, Meli M, Whitmire JM, Merrell DS, Whitelegge J, Scotti C Sci Rep. 2017 Nov 3;7(1):14479. doi: 10.1038/s41598-017-15075-4. PMID:29101342<ref>PMID:29101342</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5mq5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Asparaginase 3D structures|Asparaginase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Asparaginase]]
[[Category: Large Structures]]
[[Category: Maggi, M]]
[[Category: Merrell, D S]]
[[Category: Mittelman, S D]]
[[Category: Parmentier, J H]]
[[Category: Scotti, C]]
[[Category: Whitmire, J M]]
[[Category: Amidohydrolase]]
[[Category: Chemotherapeutic drug]]
[[Category: Hydrolase]]
[[Category: L-asparaginase]]