6v2c: Difference between revisions
New page: '''Unreleased structure''' The entry 6v2c is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Complex of mutant (K162M) of E. coli L-asparaginase II with L-Asp. Covalent acyl-enzyme intermediate and tetrahedral intermediate== | ||
<StructureSection load='6v2c' size='340' side='right'caption='[[6v2c]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6v2c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V2C 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEI:THREONINE-ASPARTIC+ESTER'>AEI</scene>, <scene name='pdbligand=QNY:O-[(3S)-3-amino-3-carboxy-1,1-dihydroxypropyl]-L-threonine'>QNY</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=6v2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v2c OCA], [https://pdbe.org/6v2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v2c RCSB], [https://www.ebi.ac.uk/pdbsum/6v2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v2c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ASPG2_ECOLI ASPG2_ECOLI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Two bacterial type II l-asparaginases, from Escherichia coli and Dickeya chrysanthemi, have played a critical role for more than 40 years as therapeutic agents against juvenile leukemias and lymphomas. Despite a long history of successful pharmacological applications and the apparent simplicity of the catalytic reaction, controversies still exist regarding major steps of the mechanism. In this report, we provide a detailed description of the reaction catalyzed by E. coli type II l-asparaginase (EcAII). Our model was developed on the basis of new structural and biochemical experiments combined with previously published data. The proposed mechanism is supported by quantum chemistry calculations based on density functional theory. We provide strong evidence that EcAII catalyzes the reaction according to the double-displacement (ping-pong) mechanism, with formation of a covalent intermediate. Several steps of catalysis by EcAII are unique when compared to reactions catalyzed by other known hydrolytic enzymes. Here, the reaction is initiated by a weak nucleophile, threonine, without direct assistance of a general base, although a distant general base is identified. Furthermore, tetrahedral intermediates formed during the catalytic process are stabilized by a never previously described motif. Although the scheme of the catalytic mechanism was developed only on the basis of data obtained from EcAII and its variants, this novel mechanism of enzymatic hydrolysis could potentially apply to most (and possibly all) l-asparaginases. | |||
Mechanism of Catalysis by l-Asparaginase.,Lubkowski J, Vanegas J, Chan WK, Lorenzi PL, Weinstein JN, Sukharev S, Fushman D, Rempe S, Anishkin A, Wlodawer A Biochemistry. 2020 May 11. doi: 10.1021/acs.biochem.0c00116. PMID:32364696<ref>PMID:32364696</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6v2c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Asparaginase 3D structures|Asparaginase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Lubkowski J]] | |||
[[Category: Wlodawer A]] | |||
Latest revision as of 11:02, 11 October 2023
Complex of mutant (K162M) of E. coli L-asparaginase II with L-Asp. Covalent acyl-enzyme intermediate and tetrahedral intermediateComplex of mutant (K162M) of E. coli L-asparaginase II with L-Asp. Covalent acyl-enzyme intermediate and tetrahedral intermediate
Structural highlights
FunctionPublication Abstract from PubMedTwo bacterial type II l-asparaginases, from Escherichia coli and Dickeya chrysanthemi, have played a critical role for more than 40 years as therapeutic agents against juvenile leukemias and lymphomas. Despite a long history of successful pharmacological applications and the apparent simplicity of the catalytic reaction, controversies still exist regarding major steps of the mechanism. In this report, we provide a detailed description of the reaction catalyzed by E. coli type II l-asparaginase (EcAII). Our model was developed on the basis of new structural and biochemical experiments combined with previously published data. The proposed mechanism is supported by quantum chemistry calculations based on density functional theory. We provide strong evidence that EcAII catalyzes the reaction according to the double-displacement (ping-pong) mechanism, with formation of a covalent intermediate. Several steps of catalysis by EcAII are unique when compared to reactions catalyzed by other known hydrolytic enzymes. Here, the reaction is initiated by a weak nucleophile, threonine, without direct assistance of a general base, although a distant general base is identified. Furthermore, tetrahedral intermediates formed during the catalytic process are stabilized by a never previously described motif. Although the scheme of the catalytic mechanism was developed only on the basis of data obtained from EcAII and its variants, this novel mechanism of enzymatic hydrolysis could potentially apply to most (and possibly all) l-asparaginases. Mechanism of Catalysis by l-Asparaginase.,Lubkowski J, Vanegas J, Chan WK, Lorenzi PL, Weinstein JN, Sukharev S, Fushman D, Rempe S, Anishkin A, Wlodawer A Biochemistry. 2020 May 11. doi: 10.1021/acs.biochem.0c00116. PMID:32364696[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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