4u3b | pdb_00004u3b

LpxC from A.Aaeolicus in complex with the MMP inhibitor 4-[[4-(4-chlorophenoxy)phenyl]sulfanylmethyl]tetrahydropyran-4-carbohydroxamic acid - compound 2

spinqualitylabelsall models 4u3b, resolution 1.34Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4u3b is a 1 chain structure with sequence from Aquifex aeolicus VF5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.34Å Ligands: 3BW, CL, IMD, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LPXC_AQUAE Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity). Publication Abstract from PubMed In the search for novel Gram-negative agents, we performed a comprehensive search of the AstraZeneca collection and identified a tetrahydropyran-based matrix metalloprotease (MMP) inhibitor that demonstrated nanomolar inhibition of UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC). Crystallographic studies in Aquifex aeolicus LpxC indicated the tetrahydropyran engaged in the same hydrogen bonds and van der Waals interactions as other known inhibitors. Systematic optimization of three locales on the scaffold provided compounds with improved Gram-negative activity. However, the optimization of LpxC activity was not accompanied by reduced inhibition of MMPs. Comparison of the crystal structure of the native product, UDP-3-O-(acyl)-glucosamine, in Aquifex aeolicus to the structure of a tetrahydropyran-based inhibitor indicates pathways for future optimization. Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.,Murphy-Benenato KE, Olivier N, Choy A, Ross PL, Miller MD, Thresher J, Gao N, Hale MR ACS Med Chem Lett. 2014 Sep 23;5(11):1213-1218. eCollection 2014 Nov 13. PMID:25408833 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-3-O-acyl-N-acetylglucosamine deacetylase UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures

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