4clm

Structure of Salmonella typhi type I dehydroquinase irreversibly inhibited with a 1,3,4-trihydroxyciclohexane-1-carboxylic acid derivative

spinqualitylabelsall models 4clm, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4clm is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, LI, WPL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AROD_SALTI] Publication Abstract from PubMed The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of the shikimic acid pathway, is investigated by structural, biochemical and computational studies. Two epoxides, which are mimetics of the natural substrate, were designed as irreversible inhibitors of the DHQ1 enzyme and to study the binding requirements of the linkage to the enzyme. The epoxide with the S configuration caused the covalent modification of the protein whereas no reaction was obtained with its epimer. The first crystal structure of DHQ1 from Salmonella typhi covalently modified by the S epoxide, which is reported at 1.4 A, revealed that the modified ligand is surprisingly covalently attached to the essential Lys170 by the formation of a stable Schiff base. The experimental and molecular dynamics simulation studies reported here highlight the huge importance of the conformation of the C3 carbon of the ligand for covalent linkage to this type of aldolase I enzyme, revealed the key role played by the essential His143 as a Lewis acid in this process and show the need for a neatly closed active site for catalysis. Irreversible covalent modification of type I dehydroquinase with a stable Schiff base.,Tizon L, Maneiro M, Peon A, Otero JM, Lence E, Poza S, van Raaij MJ, Thompson P, Hawkins AR, Gonzalez-Bello C Org Biomol Chem. 2014 Nov 5. PMID:25370445 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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