James 91社区 Professor, Department of Biochemistry
Structure of Macromolecular Machines using X-ray Crystallography and Electron Microscopy; Nonribosomal Peptide Synthetases
Francesco Bellini Life Sciences Building
3649 Promenade Sir William Osler
Office: Room 465; Lab: Room 457
Montreal, QC H3G 0B1
Tel: 514-398-2331; Lab: 514-398-3278
Fax: 514-398-2983
martin.schmeing [at] mcgill.ca
2009 鈥� Postdoc, LMB Cambridge
2004 鈥� PhD, Yale University
In the news:
How bacteria create a piggy bank for the lean times
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Research Interests
The Schmeing lab is interested in large macromolecular machines that perform important cellular processes. These enzymes often require supramolecular organization and complex architecture to function. For example, some enzymes use more than 100,000 atoms to make peptide bonds, while the proteases that break these bonds can be very small. Of course, these assemblies require regulation, processivity and fidelity, which contribute to their increased size. Our lab investigates both the manner by which cellular machines achieve these roles, and the mechanisms of their principal functions. To do this, we combine X-ray crystallography, electron microscopy and biochemical techniques.
Our main subject of study is nonribosomal peptide synthetases (NRPS). NRPSs are large macromolecular machines that catalyze peptide bond formation. Instead of making proteins, these megaenzymes produce a large variety of small molecules with important and diverse biological activity. For example, NRPSs synthesize anti-fungals, anti-bacterials, anti-virals, anti-tumourigenics, siderophores, and immunosuppressants including well-known compounds such as penicillin and cyclosporin. NRPSs use assembly line logic, with moving parts and dedicated active sites for each amino acid added to the peptide. NRPSs can be over 2 megadaltons in mass and are nature鈥檚 largest (and most fun!) enzymes.
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Selected Publications
听Sharon I, McKay G, Nguyen D, Schmeing TM. Proc Natl Acad Sci USA 2023 Feb 120(8).
Fortinez CM, Bloudoff K, Harrigan C, Sharon I, Strauss M, Schmeing TM. Nature Commun. 2022 Jan 27;13(1).
Sharon I, Haque AS, Grogg M, Lahiri I, Seebach D, Leschziner AE, Hilvert D, Schmeing TM. Nature Chem Biol. 2021 Oct;17(10).
*Alonzo DA, *Chiche-Lapierre C, Tarry MJ, Wang J, Schmeing TM. Nature Chem Biol. 2020 May; 16(5).
*Reimer JM, *Eivaskhani M, Harb I, Guarn茅 A, Weigt M, Schmeing TM. Science. 2019 Nov 8; 366(6466).
*Huguenin-Dezot N, *Alonzo DA, Heberlig GW, Mahesh M, Nguyen DP, Dornan MH, Boddy CN, **Schmeing TM, **Chin JW. Nature. 2019 Jan; 565(7737): 112-117.
Tarry MJ, Haque AS, Bui KH, Schmeing TM. X. Structure. 2017 May 2;25(5):783-793.
Bloudoff K, Fage CD, Marahiel MA, Schmeing TM. Proc Natl Acad Sci USA. 2017 Jan 3;114(1):95-100.
Bloudoff K, Alonzo DA, Schmeing TM. Cell Chem Biol. 2016 Mar 17;23(3).
Reimer JM, Aloise MN, Harrison PM, Schmeing TM. Nature. 2016 Jan 14;529(7585).
Bloudoff K, Rodionov D, Schmeing TM. Crystal Structures of the First Condensation Domain of CDA J Mol Biol. 2013 Sep 9;425(17):3137-50.
Schmeing TM*, Voorhees RM*, Kelley AC, Gao YG, Murphy FV, Weir JR, Ramakrishnan V. Science. 2009, Oct 30; 326(5953):688-94. PMID: 19833920
Schmeing TM, Ramakrishnan, V. Nature. 2009, Oct 29; 461(7268):1234-1242. PMID: 19838167
Schmeing TM, Huang KS, Strobel SA, Steitz TA. Nature. 2005 Nov 24;438(7067):520-4. PMID: 16306996