4ekr | pdb_00004ekr

T4 Lysozyme L99A/M102H with 2-Cyanophenol Bound

spinqualitylabelsall models 4ekr, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ekr is a 2 chain structure with sequence from Enterobacteria phage t4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0R0, ACT, BME, HED, SO4 Related: 4e97, 4ekp, 4ekq, 4eks Gene: E (Enterobacteria phage T4) Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Synthetic cavitands and protein cavities have been widely studied as models for ligand recognition. Here we investigate the Met102 --> His substitution in the artificial L99A cavity in T4 lysozyme as a Kemp eliminase. The resulting enzyme had k(cat)/K(M) = 0.43 M(-1) s(-1) and a (k(cat)/K(M))/k(uncat) = 10(7) at pH 5.0. The crystal structure of this enzyme was determined at 1.30 A, as were the structures of four complexes of substrate and product analogs. The absence of ordered waters or hydrogen bonding interactions, and the presence of a common catalytic base (His102) in an otherwise hydrophobic, buried cavity, facilitated detailed analysis of the reaction mechanism and its optimization. Subsequent substitutions increased eliminase activity by an additional four-fold. As activity-enhancing substitutions were engineered into the cavity, protein stability decreased, consistent with the stability-function trade-off hypothesis. This and related model cavities may provide templates for studying protein design principles in radically simplified environments. Engineering a model protein cavity to catalyze the Kemp elimination.,Merski M, Shoichet BK Proc Natl Acad Sci U S A. 2012 Sep 17. PMID:22988064 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysozyme 3D structures

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