3u1h

Crystal structure of IPMDH from the last common ancestor of Bacillus

spinqualitylabelsall models 3u1h, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u1h is a 2 chain structure with sequence from Bacsp. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: LEUB (BACSP) Activity: 3-isopropylmalate dehydrogenase, with EC number 1.1.1.85 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Thermophily is thought to be a primitive trait, characteristic of early forms of life on Earth, that has been gradually lost over evolutionary time. The genus Bacillus provides an ideal model for studying the evolution of thermophily as it is an ancient taxon and its contemporary species inhabit a range of thermal environments. The thermostability of reconstructed ancestral proteins has been used as a proxy for ancient thermal adaptation. The reconstruction of ancestral enzymes has the added advantages of demonstrable activity, which acts as an internal control for accurate inference, and providing insights into the evolution of enzymatic catalysis. Here we report the reconstruction of the structurally-complex, core metabolic enzyme LeuB (3-isopropylmalate dehydrogenase, E. C. 1.1.1.85) from the last common ancestor (LCA) of Bacillus using both maximum likelihood (ML) and Bayesian inference. ML LeuB from the LCA of Bacillus shares only 76% sequence identity with its closest contemporary homolog yet it is fully functional, thermophilic, and exhibits high values for k(cat), k(cat)/K(M) and DeltaG(double dagger) for unfolding. The Bayesian version of this enzyme is also thermophilic but exhibits anomalous catalytic kinetics. We have determined the three-dimensional structure of the ML enzyme and found that it is more closely aligned with LeuB from deeply-branching bacteria, such as Thermotoga maritima, than contemporary Bacillus species. To investigate the evolution of thermophily, three descendents of LeuB from the LCA of Bacillus were also reconstructed. They reveal a fluctuating trend in thermal evolution, with a temporal adaptation towards mesophily followed by a more recent return to thermophily. Structural analysis suggests that the determinants of thermophily in LeuB from the LCA of Bacillus and the most recent ancestor are distinct, and that thermophily has arisen in this genus at least twice via independent evolutionary paths. Our results add significant fluctuations to the broad trend in thermal adaptation previously proposed and demonstrate that thermophily is not exclusively a primitive trait, as it can be readily gained as well as lost. Our findings also demonstrate that reconstruction of complex functional Precambrian enzymes is possible, and can provide empirical access to the evolution of ancient phenotypes and metabolisms. On the Origin and Evolution of Thermophily: Reconstruction of Functional Precambrian Enzymes from Ancestors of Bacillus.,Hobbs JK, Shepherd C, Saul DJ, Demetras NJ, Haaning S, Monk CR, Daniel RM, Arcus VL Mol Biol Evol. 2011 Oct 13. PMID:21998276 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isopropylmalate dehydrogenase

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