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Chemistry Department, Seaver North, Room 212 Laboratory phone: (909) 607-7959 The Sazinsky
Research Group. Matt Sazinsky, • Click here to see a full list of
undergraduate thesis students •
Click here to see a full list of papers, attended meetings, and abstracts
Seaver North, Room 212
Laboratory phone: (909) 607-7959
Research Group. Matt Sazinsky,
• Click here to see a full list of undergraduate thesis students
• Click here to see a full list of papers, attended meetings, and abstracts
Carboxylate-bridged diiron proteins are found in almost all organisms and participate in a variety of essential biochemical functions, including hydrocarbon and fatty acid hydroxylation, tyrosyl radical generation, oxidative stress protection, O2 transport and sensing, NO reduction, iron storage, fatty acid desaturation, and ubiquinol oxidation in mitochondrial membranes. Some of these proteins, like ribonucleotide reductase (RNR) and soluble methane monooxygenase (sMMO), have received significant attention because of their biomedical, industrial, and environmental importance. The diversity of these powerful O2-utilizing dinuclear active sites rivals, if not surpasses, that of heme proteins, but diiron enzymes are found less frequently in nature. Although most diiron proteins share several structural and mechanistic features, such as strikingly similar dinuclear iron units that react with O2 and traverse peroxo and/or superoxo intermediates, it has been particularly challenging to reveal how the protein scaffold around the metal center governs reactivity. My laboratory aims to investigate the structure/function relationships responsible for the chemistry and tuning of dinuclear iron active sites by 1) focusing on proteins that carry out novel reactions using unique metal coordination spheres and by 2) re-engineering well characterized systems to perform new functions.
Mature bacterial cells can exist in two states, as free-floating planktonic cells or as densely packed biofilms on the surfaces of biological and abiotic materials. In their planktonic form, pathogenic bacteria species like Streptococcus pneumoniae, Staphalococcus aureus, Salmonella enterica and Pseudomonas aeruginosa are susceptible to antimicrobial agents. As biofilms, however, these bacteria are highly resistant to antimicrobials owing to a dense matrix of extracellular polysaccharides, proteins, and DNA known collectively as the extracellular polymeric substance (EPS). Although the general organization and function of the EPS matrix is not known, it is proposed to promote adhesion between cells and host surfaces and offer protection from hostile extracellular conditions. Because of the seemingly impenetratable nature of these films, chronic infections can result, such as in the respiratory and gastrointestinal tracts of patients with exposure to opportunistic pathogenic organisms. An understanding of biofilm development, composition and organization is essential for developing therapies aimed at disrupting their formation.
Most investigations into bacterial biofilms have focused on identifying the genetic, molecular, and physiological determinants of initiation and development. Genome-based microarray analysis and transposon mutagenesis have identified several intriguing protein targets, but, a universal set of proteins responsible for this process have not been easy to identify since different bacterial species do not always use similar machinery for biofilm formation. Structural and biochemical analysis of biofilm related proteins in well characterized model organisms will provide a clearer picture of the EPS composition as well as new avenues to combat chronic infections in a variety of pathogenic bacteria.
Camille and Henry Dreyfus Faculty Start-up Award (2007)
Current Undergraduate Research Students