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. Current agro-industrial methods for nitrile reduction are non-specific and produce environmentally hazardous by-products. An environmentally friendly alternative is being developed: natural biocatalysis by the only nitrile reductase known in biology, QueF, an oxidoreductase recently identified in the biosynthesis of the tRNA modified nucleoside queuosine. QueF active site mutants will be crystallographically studied to uncover the enzymatic mechanism and enable future engineering of mutant enzymes that biocatalyze nitrile reduction on industrial substrates. The rise of resistant infections such as MRSA and gonnorrhoeae is a health threat worldwide, warranting the need for the development of new molecular targets for antibiotics. One such target is the new bacteria-specific GTP cyclohydrolase IB (GCYH-IB), an essential enzyme in the clinically-established folate biosynthesis pathway. SSRL facilities will be used to conduct x-ray structural analysis of GCYH-IB complexed with inhibitors to enable structure-based design of new antibiotics.
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