6tzd | pdb_00006tzd

Crystal Structure of Ketosteroid Isomerase from Pseudomonas Putida (pKSI) bound to 4-Androstenedione at 280 K

spinqualitylabelsall models 6tzd, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tzd is a 2 chain structure with sequence from Pseudomonas putida. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4507Å Ligands: ASD, CL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SDIS_PSEPU Publication Abstract from PubMed How enzymes achieve their enormous rate enhancements remains a central question in biology, and our understanding to date has impacted drug development, influenced enzyme design, and deepened our appreciation of evolutionary processes. While enzymes position catalytic and reactant groups in active sites, physics requires that atoms undergo constant motion. Numerous proposals have invoked positioning or motions as central for enzyme function, but a scarcity of experimental data has limited our understanding of positioning and motion, their relative importance, and their changes through the enzyme's reaction cycle. To examine positioning and motions and test catalytic proposals, we collected "room temperature" X-ray crystallography data for Pseudomonas putida ketosteroid isomerase (KSI), and we obtained conformational ensembles for this and a homologous KSI from multiple PDB crystal structures. Ensemble analyses indicated limited change through KSI's reaction cycle. Active site positioning was on the 1- to 1.5-A scale, and was not exceptional compared to noncatalytic groups. The KSI ensembles provided evidence against catalytic proposals invoking oxyanion hole geometric discrimination between the ground state and transition state or highly precise general base positioning. Instead, increasing or decreasing positioning of KSI's general base reduced catalysis, suggesting optimized Angstrom-scale conformational heterogeneity that allows KSI to efficiently catalyze multiple reaction steps. Ensemble analyses of surrounding groups for WT and mutant KSIs provided insights into the forces and interactions that allow and limit active-site motions. Most generally, this ensemble perspective extends traditional structure-function relationships, providing the basis for a new era of "ensemble-function" interrogation of enzymes. Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray-derived conformational ensembles.,Yabukarski F, Biel JT, Pinney MM, Doukov T, Powers AS, Fraser JS, Herschlag D Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33204-33215. doi:, 10.1073/pnas.2011350117. Epub 2020 Dec 21. PMID:33376217 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ketosteroid Isomerase

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