9hit | pdb_00009hit

Structure of P167S/D240G BlaC from Mycobacterium tuberculosis

spinqualitylabelsall models 9hit, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9hit is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: CIT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLAC_MYCBO Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Displays high levels of penicillinase and cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of mycobacteria to beta-lactam antibiotics.[UniProtKB:P9WKD3] Publication Abstract from PubMed In directed evolution, enzyme activity is improved in successive generations of laboratory evolution, which can be described by a simple stepwise climb toward a peak in the fitness landscape. In a naive model of evolution, it can be assumed that each enzyme variant along this path is in a single, well-defined state that differs slightly from the previous one. We analyzed the structural changes in mutants of the beta-lactamase BlaC from Mycobacterium tuberculosis obtained via directed evolution for increased ceftazidime hydrolysis activity. Crystal structures of three successive mutants only show an increase in the dynamics of a loop that lines the active site (Omega-loop), enabling better access of the large substrate. However, NMR spectra of wild type and nine mutants of different branches of the directed evolution experiment show a much more diverse and complex picture of the conformational effects. Many mutants show micro-millisecond dynamics for certain regions and most show peak doubling, indicative of two or more conformations being populated. Thus, the straightforward climb to increased ceftazidime activity in the fitness landscape masks a complex trajectory in the conformational landscape, emphasizing the complex and epistatic interplay that single mutations can have on the structure and dynamics of enzymes. Directed evolution of a beta-lactamase samples a wide variety of conformational states.,Sun J, Timmer M, Brunle S, Boyle AL, Ubbink M Protein Sci. 2025 Nov;34(11):e70322. doi: 10.1002/pro.70322. PMID:41074874 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA