Distinguished Women In Science: Professor Rachel Austin, Barnard College, Columbia University
Distinguished Women In Science: Professor Rachel Austin, Barnard College (Host: Shoshana Williams)
**This seminar is available for in-person attendance.**
"Exploring the structure and function of alkane monooxygenase (AlkB): a key metalloenzyme in the environment."
About the Seminar
Alkane hydroxylase (AlkB) is a membrane-spanning non-heme diiron enzyme with a histidine-rich coordination site, first identified 50 years ago, responsible for catalyzing the hydroxylation of the majority of medium-to-long straight chain alkanes in the environment. AlkB catalyzes the hydroxylation of terminal alkanes, the epoxidation of alkenes, and, in selected cases, the desaturation of alkanes. Despite its importance in the global carbon cycle, relatively little is known about this large and widely-distributed class of hydroxylases. We have studied the reaction mechanism and substrate specificity of AlkB from Pseudomonas putida GPo1. More recently we have expressed and characterized the catalytic activity of AlkB from 6 additional organisms: the marine organism Alcanivorax borkumensis AP1, Dietzea cinnamea, Polaromonas naphthalenivorans, Thermomonospora curvata, Mycobacterium tuberculosis, and Fontimonas thermophila. Targeted mutations and a careful comparison of amino acid sequences have shed light on structure-function relationships in this important class of integral member monooxygenases. We are simultaneously studying the catalytic activity of two structurally-related enzymes: xylene monooxygenase and UndB. Functional studies on these non-heme diiron hydroxylases, interpreted in light of recently published crystal structures of two related enzymes, the fatty acid desaturase steroyl-CoA desaturase[1][2] and sphingolipid a-hydroxylase (Scs7p), a yeast homolog of fatty acid 2-hydroxylase (FA2H)[3], answer some questions about structure-function relationships in this important class of metalloenzymes and raise others.
[1] Bai, Y., McCoy, J. G., Levin, E. J., Sobrado, P., Rajashankar, K. R., Fox, B. G., and Zhou, M. (2015) X-ray structure of a mammalian stearoyl-CoA desaturase. Nature 524, 252–256
[2] Wang, H., Klein, M. G., Zou, H., Lane, W., Snell, G., Levin, I., Li, K., and Sang, B. C. (2015) Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate. Nat. Struct. Mol. Biol. 22, 581–585
[3] Guangyu Zhu, Mary Koszelak-Rosenblum, Sara M. Connelly, Mark E. Dumont, and Michael G. Malkowski (2015) The Crystal Structure of an Integral Membrane Fatty Acid a-Hydroxylase, J. Biol. Chem. 290, 29820-29833
About the Speaker
Rachel Narehood Austin is the Diana T. and P. Roy Vagelos Professor of Chemistry in the Department of Chemistry at Barnard College, Columbia University. Her doctoral work focused on synthetic models of high valent intermediates in the reaction cycle of cytochrome P450; work she did collaboratively with the laboratories of Alfred Trautwein in Lubeck Germany and Raymond Weiss in Strasbourg. Her laboratory has a longstanding interest in understanding the mechanisms of metalloproteins, especially those important in the global cycling of elements and neurochemistry, and developing and characterizing heterogeneous catalysts that can be used for green chemistry, biofuels upgrading, or environmental remediation.. Funding for her lab has been received from NSF, NIH, HHMI, the Merck/AAAS research fund, Pfizer, DOE, and the Dreyfus Foundation. She is the past chair (together with co-Chair Ariel Anbar) of the 2010 Environmental Bioinorganic Chemistry Gordon Research Conference and a current editorial board member of the Journal of Inorganic Biochemistry, an advisory board member for the journal Metallomics and a reviewing editor for the journal Frontiers in Microbiological Chemistry.
Image courtesy of Barnard College