4ihd

Crystal Structure of Uncleaved ThnT T282C, derivatized at the active site with EtHg

spinqualitylabelsall models 4ihd, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ihd is a 2 chain structure with sequence from Streptomyces cattleya. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: EMC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q83XN4_STRCT Publication Abstract from PubMed In the past decade, there have been major achievements in understanding the relationship between enzyme catalysis and protein structural plasticity. In autoprocessing systems, however, there is a sparsity of direct evidence of the role of conformational dynamics, which are complicated by their intrinsic chemical reactivity. ThnT is an autoproteolytically activated enzyme involved in the biosynthesis of the beta-lactam antibiotic thienamycin. Conservative mutation of ThnT results in multiple conformational states that can be observed via X-ray crystallography, establishing ThnT as a representative and revealing system for studing how conformational dynamics control autoactivation at a molecular level. Removal of the nucleophile by mutation to Ala disrupts the population of a reactive state and causes widespread structural changes from a conformation that promotes autoproteolysis to one associated with substrate catalysis. Finer probing of the active site polysterism was achieved by EtHg derivatization of the nucleophile, which indicates the active site and a neighboring loop have coupled dynamics. Disruption of these interactions by mutagenesis precludes the ability to observe a reactive state through X-ray crystallography, and application of this insight to other autoproteolytically activated enzymes offers an explanation for the widespread crystallization of inactive states. We suggest that the N --> O(S) acyl shift in cis-autoproteolysis might occur through a si-face attack, thereby unifying the fundamental chemistry of these enzymes through a common mechanism. Exploring the Role of Conformational Heterogeneity in cis-Autoproteolytic Activation of ThnT.,Buller AR, Freeman MF, Schildbach JF, Townsend CA Biochemistry. 2014 Jul 8;53(26):4273-81. doi: 10.1021/bi500385d. Epub 2014 Jun, 26. PMID:24933323 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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