Biological

Biological Chemistry seminar: Clarissa Waites, Columbia University

Thu, 2017-11-16 15:00
Location: 
Carolyn Hoff Lynch Room
"ESCRT Service: How the endocytic pathway regulates neuronal proteostasis at the synapse and beyond"

Biological Chemistry seminar: Michael Lampson, University of Pennsylvania

Thu, 2017-11-09 15:00
Location: 
Carolyn Hoff Lynch Room
“Violation of Mendel’s First Law: chromosome competition in meiosis”

Biological Chemistry seminar: Donita Brady, University of Pennsylvania

Thu, 2017-11-02 15:00
Location: 
Carolyn Hoff Lynch Room
"Copper conducted kinase signal transduction: A novel vulnerability in BRAF mutation-positive melanoma and beyond"

Biological Chemistry seminar: Erdem Karatekin, Yale University

Thu, 2017-10-19 15:00
Location: 
Carolyn Hoff Lynch Room
"How to isolate and study the ‘fusion pore’, a key intermediate during exocytotic membrane fusion" Synaptic transmission underlies neuronal communication and hormones control many physiologic processes. Neurotransmitters and hormones are released via calcium-triggered exocytosis wherein cargo-filled vesicles fuse with the plasma membrane to release their contents to the extracellular space. Both hormones and neurotransmitters are released through fluctuating, nm-sized exocytotic fusion pores that can flicker open and shut multiple times.

Biological Chemistry seminar: John Higgins, Merck and Company

Thu, 2017-09-28 15:00
Location: 
Carolyn Hoff Lynch Room
"An overview of historic and contemporary drug discovery and development…in an hour"

*Rescheduled for Today* Biology Chemistry Seminar; Dr. Ed S. Krol (University of Saskatchewan, Saskatoon, SK)

Thu, 2017-06-15 15:00 - 16:00
Speaker: 
Seminar has been Rescheduled for today at 3PM
Location: 
IAST Chemistry Complex Vagelos Building, Room 2000 231 South 34th Street
Attached Document: 

“Dimer compounds” derived from natural products. The importance of in vitro stability for the understanding biological activity

 

Megan L. Matthews

Photo: 
First Name: 
Megan L.
Last Name: 
Matthews
Official Title: 
Assistant Professor of Chemistry
Contact Information
Office Location: 
2003 Vagelos
Email: 
megamatt@sas.upenn.edu
Phone: 
215-746-4738
Twitter: 
@MegaMatthewsLab
Admin Support: 
Education: 

B.S., Chemistry, Miami University (2005)

 

Ph.D., Chemistry, The Pennsylvania State University (2011)

 

Merck Helen Hay Whitney Postdoctoral Fellow (2012–2015) and postdoctoral associate (2015–2017), Department of Molecular Medicine, The Scripps Research Institute

Research Interests: 

Research in the Matthews group unites enzymology and chemical biology to develop novel chemical proteomics technologies for the discovery of enzyme cofactors and regulatory post-translational modifications that cannot readily be predicted by gene or protein sequence.

 

Intrinsic nucleophiles abound among the proteinogenic amino acids, but, interestingly, reactive electrophiles are essentially absent. Therefore, the majority of chemical probes target nucleophilic sites to discover enzymes, inhibitors and drug therapies. However, by acquiring them through post-translational modifications, enzymes do indeed exploit diverse classes of protein-bound electrophiles for catalysis and other essential functions. Owing to this mode of acquisition, functional electrophiles are not generally predictable from sequence; thus, their breadth and prevalence remain to be found. Our group is exploring this unknown to understand the functions of reactive modifications that we have found unexpectedly on drug targets implicated in cancer and Alzheimer’s disease. Such discoveries can be uncovered using the ‘reverse-polarity’ chemical probes that we develop. We expect that this largely un-profiled half of the reactive proteome – the covalent ‘electrophilome’ – will be found to rival its 'nucleophilome' counterpart in functional diversity and disease relevance.

Selected Publications: 

The Scripps Research Institute

17.    Matthews ML*, He L, Olson EJ, Horning BD, Correia BE, Yates JR, III, Dawson PE & Cravatt BF*. “Chemoproteomic profiling and discovery of protein electrophiles in human cells.” Nat. Chem. 9, 234–243 (2017).

16.    Horning BD, Suciu RM, Ghadiri D, Ulanovskaya O, Matthews ML, Lum KM, Backus KM, Brown SJ, Rosen H & Cravatt BF. “Chemical proteomic profiling of human methyltransferases.” J. Am. Chem. Soc. 138, 13335–13343 (2016).

15.    Rajagopalan S, Wang C, Yu K, Kuzin AP, Richter F, Lew S, Miklos AE, Matthews ML, Seetharaman J, Su M, Hunt JF, Cravatt BF & Baker D. “Design of activated serine-containing catalytic triads with atomic-level accuracy.” Nat. Chem. Biol. 10, 386-391 (2014).

14.    Chang JW, Niphakis MJ, Lum KM, Cognetta AB, Wang C, Matthews ML, Niessen S, Buczynski MW, Parsons LH & Cravatt BF. “Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates.” Chem. Biol. 19, 579-588 (2012).

The Pennsylvania State University

13.    Srnec M, Wong SD, Matthews ML, Krebs C, Bollinger JM, Jr. & Solomon EI. “Electronic structure of the ferryl intermediate in the a-ketoglutarate dependent non-heme iron halogenase SyrB2: Contributions to H-atom abstraction reactivity.” J. Am. Chem. Soc. 138, 5110-5122 (2016). 

12.    Matthews ML*, Chang WC, Layne AP, Miles LA, Krebs C & Bollinger JM, Jr.* “Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase.” Nat. Chem. Biol. 10, 209-215 (2014).  

11.    Wong SD, Srnec M, Matthews ML, Liu LV, Kwak Y, Park K, Bell CB, Alp EE, Zhao JY, Yoda Y, Kitao S, Seto M, Krebs C, Bollinger JM, Jr. & Solomon EI. “Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2.” Nature 499, 320-323 (2013).

10.    Krebs C, Dassama LMK, Matthews ML, Jiang W, Price JC, Korboukh V, Li N & Bollinger JM, Jr. “Novel approaches for the accumulation of oxygenated intermediates to multi-millimolar concentrations.” Coord. Chem. Rev. 257, 234-243 (2013).

9.      Hollenhorst MA, Bumpus SB, Matthews ML, Bollinger JM, Jr. Kelleher NL & Walsh CT. “The nonribosomal peptide synthetase enzyme DdaD tethers N(b)-fumaramoyl-L-2,3-diaminopropionate for Fe(II)/a-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis.” J. Am. Chem. Soc. 132, 15773-15781 (2010).

8.      Bollinger JM, Jr. & Matthews ML. “Remote enzyme microsurgery.” Science 327, 1337-1338 (2010).

7.      Matthews ML, Neumann CS, Miles LA, Grove TL, Booker SJ, Krebs C, Walsh CT & Bollinger JM, Jr. “Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2.” Proc. Natl. Acad. Sci. USA 106, 17723-17728 (2009).

6.      Matthews ML, Krest CM, Barr EW, Vaillancourt FH, Walsh CT, Green MT, Krebs C & Bollinger JM, Jr. “Substrate-triggered formation and remarkable stability of the C–H bond-cleaving chloroferryl intermediate in the aliphatic halogenase, SyrB2.” Biochemistry 48, 4331-4343 (2009).

5.      Bollinger JM, Jr., Diao Y, Matthews ML, Xing G & Krebs C. “Myo-inositol oxygenase: a radical new pathway for O2 and C-H activation at a nonheme diiron cluster.” Dalton Trans. 905-914 (2009).

4.      Krebs C, Matthews ML, Jiang W & Bollinger JM, Jr. “AurF from Streptomyces thioluteus and a possible new family of manganese/iron oxygenases.” Biochemistry 46, 10413-10418 (2007).

3.      Fujimori DG, Barr EW, Matthews ML, Koch GM, Yonce JR, Walsh CT, Bollinger JM, Jr., Krebs C & Riggs-Gelasco PJ. “Spectroscopic evidence for a high-spin Br-Fe(IV)-oxo intermediate in the a-ketoglutarate-dependent halogenase CytC3 from Streptomyces.”  J. Am. Chem. Soc. 129, 13408-13409 (2007).

 

Miami University, 2001–2005

2.      Matthews ML, Periyannan G, Hajdin C, Sidgel TK, Bennett B & Crowder MW. “Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme.” J. Am. Chem. Soc. 128, 13050-13051 (2006).

1.      Breece RM, Costello A, Bennett B, Sigdel TK, Matthews ML, Tierney DL & Crowder MW. “A five-coordinate metal center in Co(II)-substituted VanX.” J. Biol. Chem. 280, 11074-11081 (2005).

Biological Chemistry Seminar (Leonid Mirny, MIT)

Thu, 2017-04-27 15:00 - 16:00
Location: 
Lynch Lecture Hall

Title: "Genome in 3D: models of chromosome folding"

 

Biological Chemistry Seminar (Jonas Korlach, Pacific BioSciences)

Thu, 2017-03-16 15:00 - 16:00
Location: 
Lynch Lecture Hall

Biological Chemistry Seminar (Mark Goulian, University of Pennsylvania)

Thu, 2017-03-02 15:00 - 16:00
Location: 
Lynch Lecture Hall

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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