Crystallographic structures of IlvN·Val/Ile complexes: Conformational selectivity for feedback inhibition of aceto hydroxy acid synthases

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dc.contributor.authorBansal, Akanksha
dc.contributor.authorKaranth, N. Megha
dc.contributor.authorDemeler, Borries
dc.contributor.authorSchindelin, Hermann
dc.contributor.authorSarma, Siddhartha P.
dc.date.accessioned2021-08-24T16:25:15Z
dc.date.available2021-08-24T16:25:15Z
dc.date.issued2019
dc.descriptionAccepted author manuscripten_US
dc.description.abstractConformational 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 Å) crystal structures of IlvN·Val and IlvN·Ile complexes. The valine and isoleucine ligand binding pockets are located at the dimer interface. In the IlvN·Ile complex, among residues in the binding pocket, the side chain of Cys43 is 2-fold disordered (χ1 angles of gauche– and trans). Only one conformation can be observed for the identical residue in the IlvN·Val complexes. In a reversal, the side chain of His53, located at the surface of the protein, exhibits two conformations in the IlvN·Val complex. The concerted conformational switch in the side chains of Cys43 and His53 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.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationBansal, A., Karanth, N. M., Demeler, B., Schindelin, H., & Sarma, S. P. (2019). Crystallographic structures of IlvN·Val/Ile complexes: Conformational selectivity for feedback inhibition of aceto hydroxy acid synthases. Biochemistry, 58(15), 1992-2008. https://doi.org/10.1021/acs.biochem.9b00050en_US
dc.identifier.urihttps://hdl.handle.net/10133/6010
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionIndian Institute of Science, Bangaloreen_US
dc.publisher.institutionUniversity of Texas Health Science Center at San Antonioen_US
dc.publisher.institutionUniversity of Weurzburgen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.urlhttps://doi.org/10.1021/acs.biochem.9b00050en_US
dc.subjectCrystal structureen_US
dc.subject.lcshPeptides
dc.subject.lcshProteins
dc.subject.lcshLigands
dc.subject.lcshMonomers
dc.subject.lcshMolecules
dc.titleCrystallographic structures of IlvN·Val/Ile complexes: Conformational selectivity for feedback inhibition of aceto hydroxy acid synthasesen_US
dc.typeArticleen_US
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