Clusters of Branched Aliphatic Side Chains Serve As Cores of Stability in the Native State of the HisF TIM Barrel Protein.
 

Clusters of Branched Aliphatic Side Chains Serve As Cores of Stability in the Native State of the HisF TIM Barrel Protein.

http://www.ncbi.nlm.nih.gov/corehtml...PubMedLink.gif Related Articles Clusters of Branched Aliphatic Side Chains Serve As Cores of Stability in the Native State of the HisF TIM Barrel Protein.

J Mol Biol. 2013 Jan 16;

Authors: Gangadhara BN, Laine JM, Kathuria SV, Massi F, Matthews CR

Abstract
Imidazole-3-glycerol phosphate synthase is a heterodimeric allosteric enzyme that catalyzes consecutive reactions in imidazole biosynthesis through its HisF and HisH subunits. The unusually slow unfolding reaction of the isolated HisF TIM barrel domain from the thermophilic bacteria, Thermotoga maritima, enabled an NMR-based site-specific analysis of the main-chain hydrogen bonds that stabilize its native conformation. Very strong protection against exchange with solvent deuterium in the native state was found in selected buried positions in ?-helices and pervasively in the underlying ?-strands associated with a pair of large clusters of isoleucine, leucine and valine (ILV) side chains located in the ?(7)(??)(8)(??)(1-2) and ?(2)(??)(3-6)?(7) segments of the (??)(8) barrel. The most densely packed region of the large cluster, ?(3)(??)(4-6)?(7), correlates closely with the core of stability previously observed in computational, protein engineering and NMR dynamics studies, demonstrating a key role for this cluster in determining the thermodynamic and structural properties of the native state of HisF. When considered with the results of previous studies where ILV clusters were found to stabilize the hydrogen-bonded networks in folding intermediates for other TIM barrel proteins, it appears that clusters of branched aliphatic side chains can serve as cores of stability across the entire folding reaction coordinate of one of the most common motifs in biology.


PMID: 23333740 [PubMed - as supplied by publisher]



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