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Margaret E. Glasner

Glasner, Margaret E.
Margaret E. Glasner
Associate Professor
Office:
BioBio / Room 237A
Email:
Phone:
979-458-0123
http://biochemistryweb.tamu.edu/glasner/
Undergraduate Education
B.S., B.M. University of Wyoming (1995)
Graduate Education
Postdoc. University of California, San Francisco (2003-2008)
Joined Texas A&M in 2008
Awards
NSF CAREER Award 2013

Evolution of Protein Structure and Function

Evolution is the organizing principle of biology and provides the cornerstone of our approach to understand the relationships between protein structure and function. We combine bioinformatics, biochemistry, and genetics to address fundamental questions about protein evolution, such as: What structural and mechanistic features of enzymes increase their capacity to evolve new functions? How do new metabolic pathways evolve? Are there multiple evolutionary pathways to evolve new enzyme activities?

Our primary focus is on how catalytic promiscuity serves as the raw material for evolving new enzyme activities. Catalytic promiscuity is the ability to catalyze different chemical reactions using the same active site. Many enzymes in one branch of the protein family we are studying are catalytically promiscuous, and this activity has been incorporated into new metabolic pathways more than once. Comparing the sequences and structures of these proteins will identify characteristics that permitted them to evolve the second activity.

Our goal is to use results from our research to identify fundamental evolutionary principles that can can help decipher protein structure-function relationships, predict protein functions, and improve protein engineering methods.

Recent Publications

  1. Glasner, ME. Finding enzymes in the gut metagenome. Science. 2017;355 (6325):577-578.
    doi: 10.1126/science.aam7446. PubMed PMID:28183934. .

  2. McMillan, AW, Lopez, MS, Zhu, M, Morse, BC, Yeo, IC, Amos, J et al.. Role of an active site loop in the promiscuous activities of Amycolatopsis sp. T-1-60 NSAR/OSBS. Biochemistry. 2014;53 (27):4434-44.
    doi: 10.1021/bi500573v. PubMed PMID:24955846. .

  3. Brizendine, AM, Odokonyero, D, McMillan, AW, Zhu, M, Hull, K, Romo, D et al.. Promiscuity of Exiguobacterium sp. AT1b o-succinylbenzoate synthase illustrates evolutionary transitions in the OSBS family. Biochem. Biophys. Res. Commun. 2014;450 (1):679-84.
    doi: 10.1016/j.bbrc.2014.06.034. PubMed PMID:24937446. .

  4. Odokonyero, D, Sakai, A, Patskovsky, Y, Malashkevich, VN, Fedorov, AA, Bonanno, JB et al.. Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family. Proc. Natl. Acad. Sci. U.S.A. 2014;111 (23):8535-40.
    doi: 10.1073/pnas.1318703111. PubMed PMID:24872444. PubMed Central PMC4060685.

  5. Odokonyero, D, Ragumani, S, Lopez, MS, Bonanno, JB, Ozerova, ND, Woodard, DR et al.. Divergent evolution of ligand binding in the o-succinylbenzoate synthase family. Biochemistry. 2013;52 (42):7512-21.
    doi: 10.1021/bi401176d. PubMed PMID:24060347. PubMed Central PMC3908897.

  6. Zhu, WW, Wang, C, Jipp, J, Ferguson, L, Lucas, SN, Hicks, MA et al.. Residues required for activity in Escherichia coli o-succinylbenzoate synthase (OSBS) are not conserved in all OSBS enzymes. Biochemistry. 2012;51 (31):6171-81.
    doi: 10.1021/bi300753j. PubMed PMID:22775324. .

  7. Sakai, A, Fedorov, AA, Fedorov, EV, Schnoes, AM, Glasner, ME, Brown, S et al.. Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymes. Biochemistry. 2009;48 (7):1445-53.
    doi: 10.1021/bi802277h. PubMed PMID:19220063. PubMed Central PMC2746992.

  8. Pieper, U, Chiang, R, Seffernick, JJ, Brown, SD, Glasner, ME, Kelly, L et al.. Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies. J. Struct. Funct. Genomics. 2009;10 (2):107-25.
    doi: 10.1007/s10969-008-9056-5. PubMed PMID:19219566. PubMed Central PMC2693957.

  9. Kalyanaraman, C, Imker, HJ, Fedorov, AA, Fedorov, EV, Glasner, ME, Babbitt, PC et al.. Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening. Structure. 2008;16 (11):1668-77.
    doi: 10.1016/j.str.2008.08.015. PubMed PMID:19000819. PubMed Central PMC2714228.

  10. Rakus, JF, Fedorov, AA, Fedorov, EV, Glasner, ME, Hubbard, BK, Delli, JD et al.. Evolution of enzymatic activities in the enolase superfamily: L-rhamnonate dehydratase. Biochemistry. 2008;47 (38):9944-54.
    doi: 10.1021/bi800914r. PubMed PMID:18754693. PubMed Central PMC2562705.

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