L. Mario Amzel
725 N. Wolfe Street
606 WBSB
Baltimore, MD 21205
Structural Enzymology. Enzymes play a key role in all metabolic and cell-signaling processes. Characterization of an enzyme’s biological function must include the description of its mechanisms at an atomic level. Our laboratory is deciphering the catalytic mechanism of several enzyme families, using a combination of molecular biology, biochemistry and structural Biology. Systems under study fall into two classes: enzymes that recognize or process phosphates and redox enzymes.
These systems include: pyrophosphate hydrolases, farnesyl pyrophosphate synthases, PI3K, flavoenzymes and copper hydroxylases. All experiments necessary to address mechanistic questions are carried out in the laboratory. Cloning and expression, ultrapurification, kinetic characterization, mutational analysis, mass spectrometry, crystallization, and structure determination by x-ray diffraction are some of the techniques we bring to bear to characterize the mechanisms of these enzymes. In addition to being intrinsically interesting some of these systems are being developed as targets for drug design.
Channels and transporters. We are studying the cytoplasmic control of voltage activated sodium channels and the structure and the mechanism of NIS, the sodium/iodide symporter of the thyroid gland.
Ravera S, Reyna-Neyra A, Ferrandino G, Amzel LM, Carrasco N. (2017) The sodium/iodide symporter (NIS): Molecular physiology and preclinical and clinical applications. Annu Rev Physiol. 2017 Feb 10; 79:261-289. doi: 10.1146/annurev-physiol-022516-034125. PMID: 28192058
Miller MS, Maheshwari S, McRobb FM, Kinzler KW, Amzel LM, Vogelstein B, Gabelli SB. Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design. Bioorg Med Chem 2017 Feb 15; 25(4):1481-1486. doi: 10:1016/j.bmc.2017.01.012. PMID: 28129991
Gabelli SB, Echeverria E, Alexander M, Duong-Ly KC, Chaves-Moreira D, Brower ET, Vogelstein B, and Amzel, LM. (2014) Activation of PI3Kα by physiological effectors and by oncogenic mutations: structural and dynamic effects. Biophys Rev 6:89-95 doi:10.0007/s12551-013-0131-1 PMID:25309634 [PubMed] PMCID: PMC4192660
Gabelli SB, Boto A, Kuhns VH, Bianchet MA, Farinelli F, Aripirala S, Yoder J, Jakoncie J, Tomaselli GF, and Amzel LM. (2014) Regulation of the NaV1.5 cytoplasmic domain by Calmodulin. Nat Commun. 2014 Nov 5;5:5126. doi: 10.1038/ncomms6126 PMID: 25370050
Gabelli SB, Echeverria E, Alexander M, Duong-Ly KC, Chaves-Moreira D, Brower ET, Vogelstein B, and Amzel, LM. (2014) Activation of PI3Kα by physiological effectors and by oncogenic mutations: structural and dynamic effects. Biophys Rev 6:89-95 doi:10.0007/s12551-013-0131-1 PMID:25309634 [PubMed] PMCID: PMC4192660
Nicola JP, Carrasco N, Amzel LM. (2014) Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter. Nat. Commun. DOI:10.1038/ncomms4948 PMID: 24888603 [PubMed – indexed for MEDLINE] PMCID: PMC4248369
Rudzka K, Moreno DM, Eipper B, Mains R, Estrin DA, Amzel LM. (2013) Coordination of peroxide to the Cu(M) center of peptidylglycine α-hydroxylating monooxygenase (PHM): structural and computational study. J Biol Inorg Chem 18(2):223-32. doi: 10.1007/s00775-012-0967-z. Epub 2012 Dec 18. PMID: 23247335 [PubMed – as supplied by publisher] PMCID: 23247335