1gc8

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{{STRUCTURE_1gc8| PDB=1gc8 | SCENE= }}
{{STRUCTURE_1gc8| PDB=1gc8 | SCENE= }}
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'''THE CRYSTAL STRUCTURE OF THERMUS THERMOPHILUS 3-ISOPROPYLMALATE DEHYDROGENASE MUTATED AT 172TH FROM ALA TO PHE'''
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===THE CRYSTAL STRUCTURE OF THERMUS THERMOPHILUS 3-ISOPROPYLMALATE DEHYDROGENASE MUTATED AT 172TH FROM ALA TO PHE===
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==Overview==
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The relationship between the structure and the thermostability of the 3-isopropylmalate dehydrogenase from Thermus thermophilus was studied by site-directed mutation of a single Ala residue located at the domain interface. The crystal structures of three mutant enzymes, replacing Ala172 with Gly, Val and Phe, were successfully determined at 2.3, 2.2 and 2.5 A resolution, respectively. Substitution of Ala172 by relatively 'short' residues (Gly, Val or Ile) enlarges or narrows the cavity in the vicinity of the C(beta) atom of Ala172 and the thermostablity of the enzyme shows a good correlation with the hydrophobicity of the substituted residues. Substitution of Ala172 by the 'longer' residues Leu or Phe causes a rearrangement of the domain structure, which leads to a higher thermostability of the enzymes than that expected from the hydrophobicity of the substituted residues. Mutation of Ala172 to negatively charged residues gave an unexpected result: the melting temperature of the Asp mutant enzyme was reduced by 2.7 K while that of the Glu mutant increased by 1.8 K. Molecular-modelling studies indicated that the glutamate side chain was sufficiently long that it did not act as a buried charge as did the aspartate, but instead protruded to the outside of the hydrophobic cavity and contributed to the stability of the enzyme by enhancing the packing of the local side chains and forming an extra salt bridge with the side chain of Lys175.
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(as it appears on PubMed at http://www.pubmed.gov), where 11173468 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11173468}}
==About this Structure==
==About this Structure==
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[[Category: Ipmdh]]
[[Category: Ipmdh]]
[[Category: Thermostability]]
[[Category: Thermostability]]
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Revision as of 02:04, 1 July 2008

Template:STRUCTURE 1gc8

THE CRYSTAL STRUCTURE OF THERMUS THERMOPHILUS 3-ISOPROPYLMALATE DEHYDROGENASE MUTATED AT 172TH FROM ALA TO PHE

Template:ABSTRACT PUBMED 11173468

About this Structure

1GC8 is a Single protein structure of sequence from Thermus thermophilus. Full crystallographic information is available from OCA.

Reference

Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus., Qu C, Akanuma S, Tanaka N, Moriyama H, Oshima T, Acta Crystallogr D Biol Crystallogr. 2001 Feb;57(Pt 2):225-32. PMID:11173468

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