Office: MEYR 475D
We study how proteins work via conformational changes, posttranslational modifications, and protein:protein interactions.Our research areas include proteins in the nitric oxide-sGC-cGMP pathway crucial to the cardiovascular system, nitrogen oxides modifications, non canonical protein:RNA interactions, ligand:protein interactions and novel methods to detect protein:protein interactions. Our expertise, including molecular biology, biochemistry and spectroscopy, x-ray crystallography, and small-angle x-ray scattering allows us to answer key questions regarding enzyme catalysis, inhibition, recognition, and structural plasticity. We have a strong commitment to the training of graduate, undergraduate and now high-school students.
Figure 1. X ray Crystallography
- White MR, Khan MM, Deredge D, Ross CR, Quintyn R, Zucconi BE, Wysocki VH, Wintrode PL, Wilson GM, Garcin ED. “A Dimer Interface Mutation in Glyceraldehyde 3-Phosphate Dehydrogenase Regulates its Binding to AU-rich RNA” The Journal of Biological Chemistry, 290, (2015), 1770-1785. First published on December 1 2014, doi:10.1074/jbc.M114.618165
- Seeger F, Quintyn R, Tanimoto A, Williams GJ, Tainer JA, Wysocki VH, Garcin ED. “Interfacial residues promote an optimal alignment of the catalytic center in human soluble guanylate cyclase: heterodimerization is required but not sufficient for activity” Biochemistry 53 (13), (2014), 2153-2165. PMC2823414.
- Rogers NM, Seeger F, Garcin ED, Roberts DD, Isenberg JS. “Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow” Frontiers in Physiology 5(134), , (2014) eCollection2014.
- Guan ZW, Haque MM, Wei CC, Garcin ED, Getzoff ED, Stuehr DJ “Lys842 in neuronal nitric-oxide synthase enables the autoinhibitory insert to antagonize calmodulin binding, increase FMN shielding, and suppress interflavin electron transfer” J. Biol. Chem. 285 (5), (2010), 3064-3075. PMC2823414
- Elsa Garcin, ‘La clé vers de nouveaux inhibiteurs (A novel strategy to design iNOS specific inhibitors)’Médecines Sciences, 25 (2009), 562-564.
Nature Research Highlights
- Garcin E.D., Arvai, A.S., Rosenfeld R.J., Kroeger, M.D., Crane, B.R., Andersson G., Andrews A., Hamley P.J., Mallinder P.R., Nicholls D.J., St-Gallay S.A., Tinker A.C., Gensmantel N.P., Mete A., Cheshire D.R., Connolly S., Stuehr D.J., Aberg A., Wallace A.V., Tainer J.A., Getzoff E.D. ‘Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.’ Nat. Chem. Biol. 4 (2008), 700-707. Published online: 12 October 2008; |doi:10.1038/nchembio.115
- Garcin E.D., Hosfield D.J., Haas B.J.,Björas M., Cunningham R., Tainer J.A. ‘DNA apurinic/apyrimidinic site binding and excision by endonuclease IV’ Nat. Struct. Mol. Biol. 15 (5), (2008), 515-522.
- Rameau G.A., Tukey D.S., Garcin-Hosfield E.D., Misra C., Titcombe R.F., Khatri L., Getzoff E.D., Ziff E.B. ‘Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor induces AMPA receptor trafficking and neuronal cell death.’ J. Neurosciences 27 (13), 3445-3455 (2007)
- Panda K., Haque M.M., Garcin-Hosfield E.D., Durra D., Getzoff E.D., Stuehr D.J. ‘Surface charge interactions of electron transport modules govern catalysis by nitric oxide synthase.’ J. Biol. Chem. 281(48), 36819-36827 (2006).
- Tiso M, Konas DW, Panda K, Garcin ED, Sharma M, Getzoff ED, Stuehr DJ. ‘C-terminal tail residue Arg1400 enables NADPH to regulate electron transfer in neuronal nitric oxide synthase.’ J. Biol. Chem. 280(47), 39208-39219 (2005).
- Garcin E.D., Bruns C.M., Lloyd S.J., Hosfield D.J., Tiso M., Gachhui R., Stuehr D., Tainer J.A. and Getzoff E.D. ‘Structural Basis for isozyme-specific regulation of electron transfer in Nitric Oxide Synthase.’ J. Biol. Chem. 279(36), 37918-27 (2004).
- Rosenfeld R.J., Garcin E.D., Panda K., Andersson G., Aberg A., Wallace A.V., Morris G.M., Olson A.J., Stuehr D.J., Tainer J.A. and Getzoff E.D. ‘Conformational Changes in Nitric Oxide Synthases Induced by Chlorzoxazone and Nitroindazoles: Crystallographic and Computational Analyses of Inhibitor Potency. ‘Biochemistry 41 (47), 13915-13925 (2002).
- E. Garcin, X. Vernede, C. Hatchikian, A. Volbeda, M. Frey, J.-C. Fontecilla-Camps ‘The Crystal Structure of a reduced [NiFeSe] hydrogenase provides an image of the activated catalytic center.’ Structure 7(5), 557-566 (1999).
The keynote lecture will be given by Prof. Salvador Moncada.
Speakers include Dr David Wink (NCI), Dr David Roberts (NCI), Dr Larry Keefer (NCI Frederick), Dr Jeffrey Isenberg (U. Pittsburgh), Dr Nazareno Paolocci (Hopkins Medicine), and Dr Elsa Garcin (UMBC).The symposium is free and open to the public. RSVP at NOSymposium@gmail.com for parking at UMBC.
For more information, go to: http://userpages.umbc.edu/~egarcin/NOSymposium.html
- CHEM 490: Special Topics in Chemistry – Course Website – Structural Biology. Spring 2012.
- This class is a valid upper elective for Biochem majors. Click on the link above to see the syllabus.
- CHEM 490: Special Topics in Chemistry
- CHEM490/CHEM684: Structural Biology. Spring 2011.
Here are some subjects we will explore in the class:
- Structural Biology (x-ray crystallography and other techniques to get information on the 3D structure of proteins).
- How to use this information to understand how enzymes/proteins work, interact with other proteins or DNA/RNA, how they are regulated, how it can be used for structure-based drug-design.
- We will use specific graphic programs to look at structures, interfaces and binding sites, programs to align protein sequences and analyze them.
- We will look at the tools available online for structural biology.
- We will explore specific pathways in the cell: for example the nitric oxide pathway, DNA repair pathways, and others based on recent literature.
- The course will be a combination of practical lectures (hands-on), short lectures, papers reading and discussions.
- CHEM 437: Comprehensive Biochemistry I. Fall 2010, Fall 2012.
- CHEM 690: Chemistry Seminar. The objective of this course is to improve students’ presentation skills. This course also serves as a core course for the chemistry graduate students. Fall 2009
- CHEM 713: Biochemistry/Chemistry Seminar. The objective of this course is to improve students’ scientific reporting, writing, critical thinking, and presentation skills, and to expose them to interdisciplinary research conducted by distinguished professionals from across the disciplines. This course also serves as a core course for the chemistry graduate students. Fall 2009.
- CHEM 602: Introduction to Laboratory Research. All semesters.
- CHEM 399: Tutorial Projects in Chemistry. All semesters.
- CHEM 499: Undergraduate Research. All semesters.
- CHEM 399: Tutorial Projects in Chemistry. All semesters.
- CHEM 432: Advanced Biochemistry – Special Topics in Protein Chemistry. Structural Biology. Fall 2008.
Proteins adopt precise architectures in order to perform their task in the cell. Understanding how proteins fold into a specific 3D shape helps to decipher the complex mechanisms regulating protein function. This course will cover all aspects of the structure and function of proteins, the techniques used in structural biology and applications in basic and biomedical research. The structural biology component will comprise structure prediction and modeling, folding, and experimental methods including electron microscopy, nuclear magnetic resonance, mass spectrometry, x-ray crystallography and small-angle x-ray scattering. The biology component will include topics on enzyme kinetics and mechanisms, drug design, and cellular signaling pathways relevant to health and disease. Special case studies will be discussed to highlight the relationship between structure and function and to address the key role of structural biology for rational drug design. This course will provide basic understanding of structural biology methods and their applications to solve specific problems in biology.
Our lab uses combined biochemical (kinetic assays), biophysical (circular dichroism, light scattering, fluorescence, EMSA) and structural analyses (x-ray crystallography and small-angle x-ray scattering).
We have a strong commitment to the training of graduate, undergraduate, and now high-school students.