X-RAY CRYSTALLOGRAPHIC STUDIES OF METAL-REQUIRING ENZYMES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our work at NE-CAT has focused on a number of metalloenzyme systems for which crystal quality and size make their study difficult at other synchrotron sources. A key project in the lab focuses on the binuclear manganese metalloezyme arginase, as well as enzymes that share the arginase fold such as the zinc enzymes human histone deacetylase-8 and bacterial acetylpolyamine amidohydrolase. This work additionally includes the zinc-dependent deacetylase LpxC from Yersinia enterocolitica, which catalyzes the first committed step of lipid A biosynthesis in Gram-negative bacteria. Comparisons of these metalloenzymes will ultimately reveal the chemical and structural basis for the divergent evolution of metal ion specificity and stoichiometry in the arginase fold. Additionally, our work at NE-CAT has focused on terpenoid cyclases. These are metal-requiring enzymes that catalyze the most complex organic chemical reactions in biology. Specifically, our work has focused on sesquiterpene cyclases that catalyze cyclization reactions involving substrates farnesyl diphosphate or geranylgeranyl diphosphate: epi-isozizaene synthase and copalyl diphosphate synthase.