个人简介

Degrees Ph.D. in Biological Chemistry, University of Pennsylvania

研究领域

Enzyme structure and mechanism, Macromolecular X-ray crystallography, Enzymology, Molecular Biology, Metalloenzymes, Iron-sulfur clusters, Vitamin B12, S-adenosyl-L-methionine and adenosylcobalamin radical enzymes, Posttranslational modifying enzymes, Posttranscriptional modifying enzymes, Natural product biosynthesis

We primarily use X-ray crystallography and biochemical techniques to study the structure and function of important biological systems. Our research focuses on two main areas: Challenging chemistry in natural product biosynthesis and posttranslational or posttranscriptional modifying enzymes.

近期论文

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D.P. Dowling, R.M. McCarty, A.P. Young, N.A. Bruender, V. Bandarian, C.L. Drennan. “Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism” Nat. Chem. Biol., 2014, 10, 106-112. *Selected as Cover Art Feature D.P. Dowling, J.L. Vey, A.K. Croft, C.L. Drennan. “Structural diversity in the AdoMet radical enzyme superfamily” BBA-Prot. Proteom., 2012, 1824, 1178-1195. D.P. Dowling, A.K. Croft, C.L. Drennan. “Radical use of Rossmann and TIM barrel architectures for controlling coenzyme B12 Chemistry” Annu. Rev. Biophys., 2012, 41, 403-427. M.L. Ilies, D.P. Dowling, P.M. Lombardi, D.W. Christianson. “Synthesis of a new trifluoromethylketone analogue of L-arginine and contrasting inhibitory activity against human arginase I and histone deacetylase 8” Bioorg. Med. Chem. Lett., 2011, 21, 5854-5858. M.L. Ilies, L.Di Costanzo, D.P. Dowling, K.J. Thorn, D.W. Christianson. “Binding of a,a-disubstituted amino acids to arginase suggests new avenues for inhibitor design” J. Med. Chem., 2011, 54, 5432-5443. P.M. Lombardi, K.E. Cole, D.P. Dowling, D.W. Christianson. “Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes” Curr. Opin. Struct. Biol., 2011, 21, 735-743. K.E. Cole, D.P. Dowling, M.A. Boone, A.J. Phillips, D.W. Christianson. “Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases” J. Am. Chem. Soc., 2012, 133, 12474-12477. D.P. Dowling, M.L. Ilies, K.L. Olszewski, S.P. Portugal, M.M. Mota, M. Llinás, D.W. Christianson. “Crystal structure of arginase from Plasmodium falciparum and implications for L-arginine depletion in malarial infection” Biochemistry, 2010, 49, 5600-5608. D.P. Dowling, S.G. Gattis, C.A. Fierke, D.W. Christianson. “Metal-substituted histone deacetylase structures” Biochemistry, 2010, 49, 5048-5056. D.P. Dowling, S.L. Gantt, S.G. Gattis, C.A. Fierke, D.W. Christianson. “Structural studies of histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors” Biochemistry, 2008, 47, 13554-13563. D.P. Dowling, L.Di Costanzo, H.A. Gennadios, and D.W. Christianson. “Evolution of the arginase fold and functional diversity” Cell. Mol. Life Sci., 2008, 65, 2039-2055. C.S. Higham, D.P. Dowling, J.L. Shaw, A. Cetin, C.J. Zielgler, J.R. Farrell. “Multidentate aminophenol ligands prepared with Mannich condensations” Tet. Lett. 2006, 47, 4419-4423.