Andrew M. Gulick, PhD

Many bacteria that we face are becoming resistant to the current arsenal of antibiotics that are in use in the clinic. This emphasizes the need for novel approaches to treat infections. The work in the Gulick lab is exploring novel targets and novel approaches to develop new types of antibiotics. Many drugs that are currently in use are natural products, molecules that are produced by bacteria, fungi, or plants, that have evolved to allow their host organism to survive in diverse environments. These important biological activities have enabled their use as antibacterial and anticancer agents. The Gulick lab is studying how bacteria produce these molecules to discover new ways to discover or produce new types of therapies.
In particular, the Gulick lab is interested in a family of proteins called nonribosomal peptide synthetases (NRPSs). These very large proteins use an assembly line strategy to produce peptide natural products. The group is unraveling how these enzymes work and using this information for the design and discovery of novel antibiotics. The lab is determining the structures of the proteins involved in natural product biosynthesis. In particular, they are using a rational approach to determine the structures of multiple states to develop a molecular movie of how these proteins function. They are studying multiple proteins in different states to obtain a complete understanding of the structural cycle. Additionally, these same proteins make molecules that human pathogens need to survive. Understanding how they function can allow us to block the production of these virulence factors, thereby incapacitating the bacteria as a novel strategy to treat an infection.
Select Publications:

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-Like Proteins Support a Highly Dynamic Domain Architecture. Miller BR, Drake EJ, Shi C, Aldrich CC, Gulick AM. J Biol Chem. 2016 Sep 5. pii: jbc.M116.746297. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/27597544

An Open and Shut Case: The Interaction of Magnesium with MST Enzymes. Meneely KM, Sundlov JA, Gulick AM, Moran GR, Lamb AL. J Am Chem Soc. 2016 Jul 27;138(29):9277-93. doi: 10.1021/jacs.6b05134. Epub 2016 Jul 19.
https://www.ncbi.nlm.nih.gov/pubmed/27373320

Structural and Functional Characterization of Aerobactin Synthetase IucA from a Hypervirulent Pathotype of Klebsiella pneumoniae. Bailey DC, Drake EJ, Grant TD, Gulick AM. Biochemistry. 2016 Jun 28;55(25):3559-70. doi: 10.1021/acs.biochem.6b00409. Epub 2016 Jun 16.
https://www.ncbi.nlm.nih.gov/pubmed/27253399

Structure-Function Studies of Hydrophobic Residues That Clamp a Basic Glutamate Side Chain during Catalysis by Triosephosphate Isomerase. Richard JP, Amyes TL, Malabanan MM, Zhai X, Kim KJ, Reinhardt CJ, Wierenga RK, Drake EJ,Gulick AM. Biochemistry. 2016 May 31;55(21):3036-47. doi: 10.1021/acs.biochem.6b00311. Epub 2016 May 17.
https://www.ncbi.nlm.nih.gov/pubmed/27149328

1.2 Å resolution crystal structure of the periplasmic aminotransferase PvdN from Pseudomonas aeruginosa. Drake EJ, Gulick AM. Acta Crystallogr F Struct Biol Commun. 2016 May;72(Pt 5):403-8. doi: 10.1107/S2053230X16006257. Epub 2016 Apr 22.
https://www.ncbi.nlm.nih.gov/pubmed/27139833

Structural Biology of Nonribosomal Peptide Synthetases. Miller BR, Gulick AM. Methods Mol Biol. 2016;1401:3-29. doi: 10.1007/978-1-4939-3375-4_1.
https://www.ncbi.nlm.nih.gov/pubmed/26831698

Structures of two distinct conformations of holo-non-ribosomal peptide synthetases. Drake EJ, Miller BR, Shi C, Tarrasch JT, Sundlov JA, Allen CL, Skiniotis G, Aldrich CC, Gulick AM. Nature. 2016 Jan 14;529(7585):235-8. doi: 10.1038/nature16163.
https://www.ncbi.nlm.nih.gov/pubmed/26762461
Andrew Gulick, PhD
T: 716 898 8619
gulick@hwi.buffalo.edu