Introducing Our Authors pubs.acs.org/acschemicalbiology
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HAZEM ABDELKARIM
Current position: CNRS Institute of Pharmacology and Structural Biology, Toulouse, France, EMBO Postdoctoral Fellow, since April 2013, Advisors: Dr. Virginie Gervais and Prof. Alain Milon Education: Jagiellonian University, M.Sc. in Biotechnology, 2006, Advisor: Dr. Magdalena Kosz-Vnenchak; MRC National Institute for Medical Research and University College of London, London, U.K., Ph.D. in Structural Biology, 2010, Advisor: Dr. Andres Ramos; Karolinska Institutet, Stockholm, Sweden, Postdoctoral Fellow, 2010−2012, Advisor: Prof. Ylva Lindqvist Nonscientific interests: Traveling, photography, board games My scientific interest focuses on the interactions of proteins with other macromolecules and small chemical compounds. In my research I apply structural and biophysical approaches to understand how various interactions mediate and/or modify protein function. In the current study we discovered and characterized a series of small chemical inhibitors of beta-ketoacyl acyl carrier protein reductase (FabG) from Pseudomonas aeruginosa. We showed that the inhibitors bind to a previously undescribed allosteric site and trap the protein in the catalysis-incompatible conformation. I think these inhibitors are an exciting starting point for development of novel drugs targeting bacterial fatty acid biosynthesis. Our results also raise an intriguing possibility that there is a natural ligand for the novel binding site described, which could regulate the lipids synthesis in bacteria. (Read Cukier’s article, DOI: 10.1021/cb4005063)
Image courtesy of the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago.
Education: University of Jordan, B.Sc. of Pharmacy, 2006; University of Illinois at Chicago, Ph.D. Candidate in Medicinal Chemistry, Research Advisor: Pavel A. Petukhov. Nonscientific interests: Music, reading, and sports, soccer in particular. My graduate research is focused on developing new tools that would help in the discovery of small molecules that can inhibit or disrupt in a selective and safe manner epigenetic complexes, such as HDAC3-SMRT complex. As described in our manuscript, we have been able to design a set of novel and potent photoreactive HDAC inhibitors that we call “nanorulers” to map the full length HDAC3SMRT complex in solution. Using these probes, we were able to show the existence of a novel conformation of the HDAC3-SMRT complex in solution and the ability of certain scaffolds to interact with both HDAC3 and SMRT. Furthermore, we have detected significant conformational changes within the complex that we propose to play a role in interpreting the histone code. The latter has been termed in the manuscript as the “Conformational Switch Model”. Further studies including design of “nanoprotractors” and development of novel approaches to modulate the activity of HDAC3-SMRT complex based on our findings are underway. (Read Abdelkarim’s article, DOI: 10.1021/cb400601g)
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JINDŘ ICH FANFRLIḰ
CYPRIAN D. CUKIER
́ Image courtesy of Jindřich Fanfrlik.
Current position: Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic, Junior scientist in the group of Prof. Pavel Hobza, since 2010. Education: Master of Science in Physical Chemistry, 2004; Ph.D. under supervision of Prof. Hobza, 2008, Faculty of Science, Charles University, Prague, Czech Republic. Image courtesy of Cyprian D. Cukier. © 2013 American Chemical Society
Published: November 15, 2013 2347
dx.doi.org/10.1021/cb4008088 | ACS Chem. Biol. 2013, 8, 2347−2348
ACS Chemical Biology
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Nonscientific interests: Trekking, tigers, mountains, martial arts, playing guitar. I’m interested in computational treatment of noncovalent interactions in protein−ligand complexes. For my Ph.D. research, I studied carborane interactions with biomolecule and specifically metallacarborane inhibitors of HIV-1 protease. Currently, I’m working on the semiempirical quantum mechanical scoring function for protein−ligand affinities. In this manuscript, we show that it is possible to tune the strength of a halogen bond in a protein−ligand complex and modulate thus the aldose reductase inhibition. We combine advanced binding free energy calculations with ultrahigh-resolution X-ray crystallography and IC50 measurements to obtain a deep insight ́ article DOI: into the studied inhibition process. (Read Fanfrlik’s 10.1021/cb400526n)
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Introducing Our Authors
SATHYA DEV UNUDURTHI
Image courtesy of Sathya Dev Unudurthi.
Current position: Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Postdoctoral Fellow, 2013−Current, Advisor: Assistant Professor Thomas J. Hund Education: Jawaharlal Nehru Technological University, India, B.Tech. in Biotechnology, 2006; National University of Singapore, Ph.D. in Biological Sciences, 2012, Advisor: Assistant Professor Kim Chu Young Nonscientific interests: Outdoor sports, gadgets, traveling, meditation, entrepreneurship An important causal factor of several human autoimmune disorders (e.g., type 1 diabetes, celiac disease, rheumatoid arthritis) is the association of antigenic peptides to a particular class II major histocompatibility complex (MHC) protein. An intriguing structural feature of all peptide-class II MHC complexes is that the bound peptides, irrespective of length and sequence, adopt a polyproline II (PPII) helical backbone conformation. PP II helix structure has approximately 3 residues per turn and is characterized by lack of intramolecular hydrogen bonds. My research was focused on investigating the influence of peptide PPII content on peptide-MHC association. Our study expands the limited amount of knowledge currently available on the effect of peptide secondary structure on class II MHC binding. (Read Unudurthi’s article, DOI: 10.1021/cb400594q)
LAURENS LINDENBURG
Image courtesy of Laurens Lindenburg.
Current position: Eindhoven University of Technology (Netherlands), Department of Biomedical Engineering, Laboratory of Chemical Biology; graduate student with Dr. M. Merkx. Education: Cardiff University, U.K., B.Sc. in Microbiology; VU University Amsterdam, M.Sc. in Biomolecular Sciences. Nonscientific interests: Playing rugby, traveling, and reading. My Ph.D. research is focused on the rational design of FRET-based genetically encoded sensors for small molecules and ions, to ultimately unravel the cell’s signaling networks. In these sensors, a fluorescent protein (FP) pair changes its emission when the ligand of interest binds a receptor domain. Elucidation of spatiotemporal correlations between signaling pathways requires differently colored sensors; yet red-shifted sensors developed thus far tend to perform poorly. Exploiting red FPs’ tendency to form oligomers, we introduced dimerizing mutations in the mOrange/mCherry FRET pair so that it formed an intramolecular dimer that could be disrupted upon binding of the ligand of interest, resulting in a much improved sensor response. I found the rational approach to sensor design fulfilling, and I hope that others will benefit from this new red FRET pair. (Read Lindenburg’s article, DOI: 10.1021/cb400427b) 2348
dx.doi.org/10.1021/cb4008088 | ACS Chem. Biol. 2013, 8, 2347−2348
