6zt4

Pentapeptide repeat protein MfpA from Mycobacterium smegmatis

spinqualitylabelsall models 6zt4, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6zt4 is a 2 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.77Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MFPA_MYCS2 Publication Abstract from PubMed DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrase-targeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Here, we show that Mycobacterium smegmatis MfpA (MsMfpA) inhibits negative supercoiling by M. smegmatis gyrase (Msgyrase) in the absence of FQs, while in their presence, MsMfpA decreases FQ-induced DNA cleavage, protecting the enzyme from these drugs. MsMfpA stimulates the ATPase activity of Msgyrase by directly interacting with the ATPase domain (MsGyrB47), which was confirmed through X-ray crystallography of the MsMfpA-MsGyrB47 complex, and mutational analysis, demonstrating that MsMfpA mimics a T (transported) DNA segment. These data reveal the molecular mechanism whereby MfpA modulates the activity of gyrase and may provide a general molecular basis for the action of other pentapeptide-repeat proteins. The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic.,Feng L, Mundy JEA, Stevenson CEM, Mitchenall LA, Lawson DM, Mi K, Maxwell A Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). pii: 2016705118. doi:, 10.1073/pnas.2016705118. PMID:33836580 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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