Copper amine oxidases are oxygen utilizing enzymes which are used by single celled organisms to free ammonia from amines during growth in nitrogen-limited conditions. Though both bacterial and eukaryotic copper amine oxidases have been studied, there have been no amine oxidases identified in archaea. We would like to understand the origin and evolution of enzymes which utilize oxygen as a substrate using amine oxidases as a frame of reference. Rapidly expanding protein and nucleic acid sequence information should make this a more tractable question. Additionally, although there is less than 10% identity among amine oxidases based on primary sequence, recent crystal structures of three amine oxidases, including eukaryotic and prokaryotic enzymes, show high conservation of structure. The interactive software programs of the Computer Graphics Lab will allow us to correlate primary sequence homology with areas which are important either structurally or catalytically. This will be particularly helpful in looking for amine oxidases which are evolutionarily distant. Lysyl oxidase is a mammalian enzyme which is involved in the cros-linking of collagen and elastin during the biosynthesis of connective tissue. The enzyme contains both a copper cofactor and an organic cofactor formed by the cross-linking of a modified tyrosine to a lysine in the active site of the protein. We are looking for other enzymes which contain LTQ as a cofactor by using primary sequence information from the mammalian lysyl oxidases and knowledge of the residues required to form the cofactor. We have begun working on gathering sequences for each aspect of this project, and will begin correlating sequence and structure using MidasPlus.
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