Dr. Marcos Alcantara de Oliveira | |
University of the Incarnate Word Feik School of Pharmacy Pharmaceutical Sciences Associate ProfessorAppointed: 2006 |  |
QualificationsPh.D., Biochemistry/Structural Biology, 1993. M.S., University of Sao Paulo, Applied Physics, 1986. B.S., University of Campinas, Physics, 1984. Postdoc, Structural Enzymology PLP Enzymes. Expertise and Research InterestsMy laboratory in collaboration with Dr. Robert Perry and Dr. Jackie Fetherston have uncovered a novel link between Polyamines and Biofilm. We are working to unravel the mechanistic details. The exciting implications lie in the potential that this mechanistic link may also exist in other bacterial pathogens.
In collaboration with Dr. Robert Perry and Jackeline Fetherston we are investigating the function of polyamines in Yersinia pestis to develop a mechanistic understanding of how polyamines regulate biofilm in Y. pestis.
In collaboration with Dr. Patrick Woster we are working to identify small molecular weight compounds that interfere with polyamine metabolism in bacteria.
In collaboration with Dr. John Hart UTHSC-San Antonio we are working on the structural Biology of polyamine metabolism using structure-based-drug design approach to identify novel antibiotics.
In partnership with Dr. Mary Pat Moyer of INCELL we have initiated a drug discovery project involving Dr. Patrick Woster, and Dr. Lawrence Marton of Progen.
Our overall goal is the investigation of a novel mechanism of biofilm regulation involving polyamines. Other ExpertiseThe technical expertise in the lab involves protein expression purification crystallization, structural determination utilizing X-ray crystallography and functional kinetic characterization. Our lab has also gained expertise in molecular biology of Y. pestis Future ResearchMechanistic investigation of the role of polyaminess in signaling mechanism in bacteria.
Structural Biology and proteins engineering of polyketide and post-polyketide enzymes involved in the synthesis of natural products.
Structure biology of Poly(ADP-Ribosylation) and its use in the desing of novel therapeutic compounds against cancer. Industrial RelevanceNovel antibiotics and biodefense agents are necessary due to resistance that is developed in bacteria. Several companies also have interest in novel antibiotics not only for medical purposes but in the food processing industry and medical implants as well.
PARP-1 inhibitors are currently being developed by Agouron and Guilford Pharmaceuticals as cancer chemosensitizing agents and for tretment of strokes respectively. KeywordsCOS Keywords:Antimicrobial Resistance, Applied Physics, Biochemistry, Biofilms, Crystallography, Enzymology, Molecular Microbiology, Pharmaceuticals, Pharmacy, Structural Biology.Additional Terms:ADP Ribosylation, Biofilm, Crystallography, Enzymology, FAD-dependent Monooxygenases, Polyamines, Polyketide, Protein Structure/Function, Rapid-kinetics, Yersinia Pestis.Languages(Reading, Writing, Speaking)English: (Fluent, Fluent, Fluent) Portuguese: (Fluent, Fluent, Fluent) Spanish: (Basic, Basic, Basic) MembershipsAmerican Association for Cancer Research American Association for the Advancement of Science American Association of Colleges of Pharmacy American Association of Pharmaceutical Scientists American Chemical Society American Crystallographic Association Protein Society Honors and Awards2003-2005,
Wethington Award,
University of Kentucky,
Faculty productivity
1999-2000,
New Investigator Award,
American Association of Colleges of Pharmacy,
University of Kentucky,
Pharmaceutical Sciences
1984-1986,
MS Fellowship,
FAPESP - Fundacao de Amparo a Pesquisa do Estado de Sao Paulo,
Universidade de Sao Paulo (USP), IFQSC,
Crystallography
Previous Positions1999-2006, Assistant Professor,
University of Kentucky,
College of Pharmacy,
Pharmaceutical Sciences
1999-2006, Assistant Professor,
University of Kentucky,
Medical Research Centers,
Center for Structural Biology
1999-2006, Assistant Professor,
University of Kentucky,
Medical Research Centers,
Lucille Parker Markey Cancer Center
1993-1998, Postdoctoral Fellow,
University of Texas at Austin,
Arts & Sciences,
Chemistry and Biochemistry
PatentsPARP-1 targeting for designing chemo/radio sensitizing agents,
Patent Number: 10/163587,
2006,
Institution,
United States of America.
 Funding Received- Kentucky Lung Cancer Research Grant:
A novel Chemo/Radio sensitizing Target: PARP-1 activation domain,
$300,
Oct 1, 2001
to Sep 30, 2004.
- :
Structure function of Poly(ADP-Ribose) Glycohydrolase,
$20,000,
May 1999
to May 2000.
- UK-Medical Center Research:
,
$16,000,
Jul 2000
to Jun 2001.
- American Association of Colleges of Pharmacy:
New Investigator Award,
$10,000,
Dec 1999
to Dec 2000.
- South East Regional Center for Excellence in Biodefense and Emerging Infectious Disease, Southeast Regional (SECEB), NIH:
Targeting Polyamines for biodefense,
$200,000,
2004
to 2006.
Publications- Oliveira, M. A., McConnel, M., Rohr, J. (2008) A model for the FAD dependent Baeyer-Villiger monnoxygenase (BVMO) type I of MtmOIV from the biosynthetic pathway of mithramicyn from streptomyces argillaceus: evidence for a GR2 fold, Unpublished
- Counts, K, Wong, I., Oliveira, M. A. (2007) Investigating the geminal diamine intermediate of Yersinia pestis arginine decarboxylase with substrate, product and inhibitors using single wavelength stopped-flow spectroscopy, Biochemistry
- Wortham, B. W., Patel, C. N., Oliveira, M. A. (2007) Polyamines in bacteria: pleiotropic effects yet specific mechanisms, Adv Exp Med Biol, 603, 116-115
- Patel, CN (2006) Polyamines are essential for the formation of plague biofilm, Journal of Bacteriology, 188 (7), 2355-63
- Gibson, M, Nur-e-alam M., Oliveira, M. A., Rohr (2005) Characterization of Kinetics and Products of the Baeyer-Villiger oxygenase MtmOIV a key enzyme of the biosynthetic pathway toward the natural product anticancer drug mithramycin from streptomyces argillaceus, J. Am. Chem. Soc., 127 (50), 17594-5
- Johnsamuel J, Ericksson S, Oliveira MA, Tjarks W, Docking Simulation With Purine Nucleoside Specific Homology Model of Deoxycytidine Kinase, a Target for Anticancer and Antiviral Therapy, Bioorg Med. Chem, 13(4160), 4170, 1 Jul 2005
- Patel CN, Koh DW, Jacobson MK, Oliveira MA, Identification of Three Critical Acidic Residues of Poly(ADP-ribose)
Glycohydrolase Involved in Catalysis: Determining the PARG Catalytic
Domain., The Biochemical Journal, 388(Pt 2), 493-500, Jun 2005
 - Wang , C, Gibson, M, Rohr, J, Oliveira (2005) Crystallization and X-ray diffraction properties of Baeyer-Villiger monooxygenase MtmOIV from mithramycin biosynthetic pathway in Streptomyces argillaceus, Acta Cryst F, F61 (1023), 1026
- Patel CN, Adcock RS, Sell KG, Oliveira MA., Crystallization, X-ray diffraction and oligomeric characterization of arginine decarboxylase from Yersinia pestis, a key polyamine biosynthetic enzyme, Acta Crystallogr D Biol Crystallogr., 60, 2396-8, Dec 2004
- Paul B.Balbo,Chandra N.Patel,Korie G.Sell,Robert S.Adcock,Sundar Neelakantan,Peter A.Crooks,and Marcos A.Oliveira, Spectrophotometric and Steady-State Kinetic Analysis of the Biosynthetic Arginine Decarboxylase of Yersinia pestis Utilizing Arginine Analogues as Inhibitors and Alternative Substrates†, Biochemistry, 42, 15189-15196, 5 Dec 2003
- Cho H, Oliveira MA, Tai HH, Critical residues for the coenzyme specificity of NAD(+)-dependent
15-hydroxyprostaglandin dehydrogenase, Archives of Biochemistry and Biophysics, 419(2), 139-46, November 2003
 - Koh DW, Patel CN, Ramsinghani S, Slama JT, Oliveira MA, Jacobson MK., Identification of an inhibitor binding site of poly(ADP-ribose) glycohydrolase, Biochemistry, 42(17), 4855-63., 6 May 2003
- Remsing LL, Gonzalez AM, Nur-e-Alam M, Fernandez-Lozano MJ, Brana AF, Rix U, Oliveira MA, Mendez C, Salas JA, Rohr J, Mithramycin SK, a novel antitumor drug with improved therapeutic index,
mithramycin SA, and demycarosyl-mithramycin SK: three new products
generated in the mithramycin producer Streptomyce, Journal of the American Chemical Society, 125(19), 5745-53, May 2003
 - Balbo P, Oliveira M., Crystallization and preliminary X-ray data of the alpha2 varepsilon 2 subcomponent of the acetyl-CoA decarbonylase/synthase multienzyme complex from Methanosarcina thermophila, Acta Crystallographica, Section D: Biological Crystallography, 59, 721-723, April 2003
- Ching TT, Lin HP, Yang CC, Oliveira M, Lu PJ, Chen CS., Specific binding of the C-terminal Src homology 2 domain of the p85alpha subunit of phosphoinositide 3-kinase to phosphatidylinositol 3,4,5-trisphosphate. Localization and engineering of the phosphoin, Journal of Biological Chemistry, 276(47), 43932-8., 23 Nov 2001
- Almrud JJ, Oliveira MA, Kern AD, Grishin NV, Phillips MA, Hackert ML, Crystal structure of human ornithine decarboxylase at 2.1 A resolution: structural insights to antizyme binding, Journal of Molecular Biology, 295(1), 7-16, 2000
 - Kern AD, Oliveira MA, Coffino P, Hackert ML, Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases, Structure With Folding and Design, 7(5), 567-81, May 1999
 - Knapp JE, Oliveira MA, Xie Q, Ernst SR, Riggs AF, Hackert ML, The structural and functional analysis of the hemoglobin D component from chicken, Journal of Biological Chemistry, 274(10), 6411-20, 1999
 - Oliveira MA, Carroll D, Davidson L, Momany C, Hackert ML, The GTP effector site of ornithine decarboxylase from Lactobacillus 30a: kinetic and structural characterization, Biochemistry, 36(51), 16147-54, 1997
 - Hadfield AT, Lee Wm, Zhao R, Oliveira MA, Minor I, Rueckert RR, Rossmann MG, The refined structure of human rhinovirus 16 at 2.15 A resolution: implications for the viral life cycle, Structure, 5(3), 427-41, 1997
 - Kern A, Oliveira MA, Chang NL, Ernst SR, Carroll DW, Momany C, Minard K, Coffino P, Hackert ML, Crystallization of a mammalian ornithine decarboxylase, Proteins, 24(2), 266-8, February 1996
 - Hadfield AT, Oliveira MA, Kim KH, Minor I, Kremer MJ, Heinz BA, Shepard D, Pevear DC, Rueckert RR, Rossmann MG, Structural studies on human rhinovirus 14 drug-resistant compensation mutants, Journal of Molecular Biology, 253(1), 61-73, 1995
 - Rossmann MG, Olson NH, Kolatkar PR, Oliveira MA, Cheng RH, Greve JM, McClelland A, Baker TS, Crystallographic and cryo EM analysis of virion-receptor interactions, Archives of Virology. Supplementum, 9, 531-41, 1994
 - Oliveira MA, Zhao R, Lee WM, Kremer MJ, Minor I, Rueckert RR, Diana GD, Pevear DC, Dutko FJ, McKinlay MA, The structure of human rhinovirus 16, Structure, 1(1), 51-68, 1993
 - Kim KH, Willingmann P, Gong ZX, Kremer MJ, Chapman MS, Minor I, Oliveira MA, Rossmann MG, Andries K, Diana GD, A comparison of the anti-rhinoviral drug binding pocket in HRV14 and HRV1A, Journal of Molecular Biology, 230(1), 206-27, 1993
 - Olson NH, Kolatkar PR, Oliveira MA, Cheng RH, Greve JM, McClelland A, Baker TS, Rossmann MG, Structure of a human rhinovirus complexed with its receptor molecule, Proceedings of the National Academy of Sciences (USA), 90(2), 507-11, 1993
 - Mallamo JP, Diana GD, Pevear DC, Dutko FJ, Chapman MS, Kim KH, Minor I, Oliveira M, Rossmann MG, Conformationally restricted analogues of disoxaril: a comparison of the
activity against human rhinovirus types 14 and 1A, Journal of Medicinal Chemistry, 35(25), 4690-5, December 1992
 - Giranda VL, Heinz BA, Oliveira MA, Minor I, Kim KH, Kolatkar PR, Rossmann MG, Rueckert RR, Acid-induced structural changes in human rhinovirus 14: possible role in uncoating, Proceedings of the National Academy of Sciences (USA), 89(21), 10213-7, 1992
 - Kolatkar PR, Oliveira MA, Rossmann MG, Robbins AH, Katti SK, Hoover-Litty H, Forte C, Greve JM, McClelland A, Olson NH, Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1, Journal of Molecular Biology, 225(4), 1127-30, 1992
 - Badger J, Krishnaswamy S, Kremer MJ, Oliveira MA, Rossmann MG, Heinz BA, Rueckert RR, Dutko FJ, McKinlay MA, Three-dimensional structures of drug-resistant mutants of human rhinovirus 14, Journal of Molecular Biology, 207(1), 163-74, 1989
 - Badger J, Minor I, Oliveira MA, Smith TJ, Rossmann MG, Structural analysis of antiviral agents that interact with the capsid of human rhinoviruses, Proteins, 6(1), 1-19, 1989
 - Badger J, Minor I, Kremer MJ, Oliveira MA, Smith TJ, Griffith JP, Guerin DM, Krishnaswamy S, Luo M, Rossmann MG, Structural analysis of a series of antiviral agents complexed with human rhinovirus 14, Proceedings of the National Academy of Sciences (USA), 85(10), 3304-8, May 1988

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