6oz8

Crystal structure of Mtb aspartate decarboxylase in active form

spinqualitylabelsall models 6oz8, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6oz8 is a 12 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: PYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAND_MYCTU Catalyzes the pyruvoyl-dependent decarboxylation of aspartate to produce beta-alanine (By similarity). Publication Abstract from PubMed Pyrazinamide has been a mainstay in the multidrug regimens used to treat tuberculosis. It is active against the persistent, non-replicating mycobacteria responsible for the protracted therapy required to cure tuberculosis. Pyrazinamide is a pro-drug that is converted into pyrazinoic acid (POA) by pyrazinamidase, however, the exact target of the drug has been difficult to determine. Here we show the enzyme PanD binds POA in its active site in a manner consistent with competitive inhibition. The active site is not directly accessible to the inhibitor, suggesting the protein must undergo a conformational change to bind the inhibitor. This is consistent with the slow binding kinetics we determined for POA. Drug-resistant mutations cluster near loops that lay on top of the active site. These resistant mutants show reduced affinity and residence time of POA consistent with a model where resistance occurs by destabilizing the closed conformation of the active site. The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD.,Sun Q, Li X, Perez LM, Shi W, Zhang Y, Sacchettini JC Nat Commun. 2020 Jan 17;11(1):339. doi: 10.1038/s41467-019-14238-3. PMID:31953389 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aspartate decarboxylase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA