Marcia Newcomer

George C. Kent Professor
BMB Division

PhD: Rice University, 1979

Phone: 225-578-7383
Lab Phone: 225-578‐7385
Office: 505 Choppin Hall
Lab: 501/503 Choppin Hall
E-mail: [email protected]

Area of Interest

The ability of the cell to respond to its environment depends on the effective coordination and/or integration of metabolic pathways. For those pathways that involve the biosynthesis of lipophilic signaling molecules, their coordination may be exceptionally challenging in terms of substrate acquisition and specificity, as hydrophobic compounds will partition into the membrane phase, and active sites that recognize bulky hydrophobic substrates might be inherently promiscuous. In order to understand how specificity is achieved in the context of the cell, and how the channeling of intermediates might enhance specificity, we have focused our recent efforts on the structural biology of enzymes involved in the biosynthesis of compounds derived from arachidonic acid released from the membrane by the action of phospholipases. These compounds serve as the precursor for prostaglandins, leukotrienes, thromboxanes, and other biologically active eicosanoids, and the enzymes involved in their biosynthesis represent drug targets, or avenues for the preparation of related compounds for pharmacological uses. In our laboratory we address questions of the regio- and stereo- specificity of these biosynthetic enzymes, as well as how soluble enzymes in this pathway acquire insoluble substrates.

Selected Publications

Haeggstrom JZ, Newcomer ME, Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics. Annual Review of Pharmacology and Toxicology. 2022 Jan 20:63:407-428

Gilbert NC, Newcomer ME, Werz O. Untangling the web of 5-lipoxygenase-derived products from a molecular and structural perspective: The battle between pro- and anti-inflammatory lipid mediators. Biochem Pharmacol. 2021 Nov;193:114759.

Gilbert NC, Gerstmeier J, Schexnaydre EE, Börner F, Garscha U, Neau DB, Werz O, Newcomer ME. Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products. Nat Chem Biol. 2020 Jul;16(7):783-790.

Gerstmeier J, Newcomer ME, Dennhardt S, Romp E, Fischer J, Werz O, Garscha U. 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation. FASEB J. 2016 May;30(5):1892-900.

Newcomer ME, Brash AR. The structural basis for specificity in lipoxygenase catalysis. Protein Sci. 2015 Mar;24(3):298-309.