6v28 | pdb_00006v28

Complex of double mutant (T89V,K162T) of E. coli L-asparaginase II with L-Asp

spinqualitylabelsall models 6v28, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6v28 is a 4 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: AEI, GOL, IMD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ASPG2_ECOLI 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Asparaginase 3D structures

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