6yrs

Structure of a new variant of GNCA ancestral beta-lactamase

spinqualitylabelsall models 6yrs, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6yrs is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: ACT, EDO, PEG, PGE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed TEM-1 beta-lactamase degrades beta-lactam antibiotics with a strong preference for penicillins. Sequence reconstruction studies indicate that it evolved from ancestral enzymes that degraded a variety of beta-lactam antibiotics with moderate efficiency. This generalist to specialist conversion involved more than 100 mutational changes, but conserved fold and catalytic residues, suggesting a role for dynamics in enzyme evolution. Here, we develop a conformational dynamics computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism. By deliberately weighting and altering the conformational dynamics of a putative Precambrian beta-lactamase, we engineer enzyme specificity that mimics the modern TEM-1 beta-lactamase with only 21 amino acid replacements. Our conformational dynamics design thus re-enacts the evolutionary process and provides a rational allosteric approach for manipulating function while conserving the enzyme active site. Hinge-shift mechanism as a protein design principle for the evolution of beta-lactamases from substrate promiscuity to specificity.,Modi T, Risso VA, Martinez-Rodriguez S, Gavira JA, Mebrat MD, Van Horn WD, Sanchez-Ruiz JM, Banu Ozkan S Nat Commun. 2021 Mar 25;12(1):1852. doi: 10.1038/s41467-021-22089-0. PMID:33767175 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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