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Crystallographic Structures of IlvN center dot Val/Ile Complexes: Conformational Selectivity for Feedback Inhibition of Aceto Hydroxy Acid Synthases

Bansal, Akanksha and Karanth, N Megha and Demeler, Borries and Schindelin, Hermann and Sarma, Siddhartha P (2019) Crystallographic Structures of IlvN center dot Val/Ile Complexes: Conformational Selectivity for Feedback Inhibition of Aceto Hydroxy Acid Synthases. In: BIOCHEMISTRY, 58 (15). pp. 1992-2008.

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Official URL: http://dx.doi.org/ 10.1021/acs.biochem.9b00050

Abstract

Conformational factors that predicate selectivity for valine or isoleucine binding to IlvN leading to the regulation of aceto hydroxy acid synthase I (AHAS I) of Escherichia coli have been determined for the first time from high-resolution (1.9-2.43 angstrom) crystal structures of IlvN center dot Val and IlvN center dot Ile complexes. The valine and isoleucine ligand binding pockets are located at the dimer interface. In the IlvN center dot Ile complex, among residues in the binding pocket, the side chain of Cys(43) is 2-fold disordered (chi(1) angles of gauche(-) and trans). Only one conformation can be observed for the identical residue in the IlvN center dot Val complexes. In a reversal, the side chain of His(53), located at the surface of the protein, exhibits two conformations in the IlvN center dot Val complex. The concerted conformational switch in the side chains of Cys(43) and His(53) may play an important role in the regulation of the AHAS I holoenzyme activity. A significant result is the establishment of the subunit composition in the AHAS I holoenzyme by analytical ultracentrifugation. Solution nuclear magnetic resonance and analytical ultracentrifugation experiments have also provided important insights into the hydrodynamic properties of IlvN in the ligand-free and -bound states. The structural and biophysical data unequivocally establish the molecular basis for differential binding of the ligands to IlvN and a rationale for the resistance of IlvM to feedback inhibition by the branched-chain amino acids.

Item Type: Journal Article
Additional Information: copyright for this article belongs to AMER CHEMICAL SOC
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Depositing User: Id for Latest eprints
Date Deposited: 29 May 2019 09:18
Last Modified: 29 May 2019 09:18
URI: http://eprints.iisc.ac.in/id/eprint/62627

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