6nw4

Evolution of a computationally designed Kemp eliminaseEvolution of a computationally designed Kemp eliminase

Structural highlights 6nw4 is a 1 chain structure with sequence from Sacs2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Gene: trpC, SSO0895 (SACS2) Activity: Indole-3-glycerol-phosphate synthase, with EC number 4.1.1.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Temperature influences the reaction kinetics and evolvability of all enzymes. To understand how evolution shapes the thermodynamic drivers of catalysis, we optimized the modest activity of a computationally designed enzyme for an elementary proton-transfer reaction by nearly 4 orders of magnitude over 9 rounds of mutagenesis and screening. As theorized for primordial enzymes, the catalytic effects of the original design were almost entirely enthalpic in origin, as were the rate enhancements achieved by laboratory evolution. However, the large reductions in DeltaH() were partially offset by a decrease in TDeltaS() and unexpectedly accompanied by a negative activation heat capacity, signaling strong adaptation to the operating temperature. These findings echo reports of temperature-dependent activation parameters for highly evolved natural enzymes and are relevant to explanations of enzymatic catalysis and adaptation to changing thermal environments. Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme.,Bunzel HA, Kries H, Marchetti L, Zeymer C, Mittl PRE, Mulholland AJ, Hilvert D J Am Chem Soc. 2019 Jul 19. doi: 10.1021/jacs.9b02731. PMID:31282667 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Indole-3-glycerol phosphate synthase

spinqualitylabelsall models 6nw4, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image