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James Sacchettini

Sacchettini, James
James Sacchettini
Professor of Biochemistry and Biophysics and of Chemistry; Wolfe-Welch Chair in Science
Office:
ILSB / Room 2138A
Email:
Phone:
979-862-7636
http://www.sacclab.com
Undergraduate Education
B.A St. Louis University (1980)
Graduate Education
Ph.D. Washington University, St. Louis (1987)
Postdoc. Washington University, St. Louis (1987-89)
Professor. Albert Einstein College of Medicine
Joined Texas A&M in 1996

Crystallography / Drug Design

My lab uses X-ray crystallography to better understand the relationship between proteins and ligands. Tiny differences in the structure of a molecule can radically change the interaction between a protein and ligand and we are only begining to understand how many factors play a role in this interaction. By manipulating the individual components of a compound it is possible to create a chemical that binds to the protein better than the natural substrate, and prevent the natural reaction from occurring. This is the basis for rational drug design. Our efforts have lead us to collaborations with other labs and scientists in many disciplines as our approach to directed compound design has applications not only in basic research but also in pesticide development, health research and clinical research.

Recent Publications

  1. Puckett, S, Trujillo, C, Wang, Z, Eoh, H, Ioerger, TR, Krieger, I et al.. Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2017;114 (11):E2225-E2232.
    doi: 10.1073/pnas.1617655114. PubMed PMID:28265055. .

  2. Zhu, M, Harshbarger, WD, Robles, O, Krysiak, J, Hull, KG, Cho, SW et al.. A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids. Bioorg. Med. Chem. 2017; :.
    doi: 10.1016/j.bmc.2017.01.020. PubMed PMID:28236510. .

  3. Gomez, JE, Kaufmann-Malaga, BB, Wivagg, CN, Kim, PB, Silvis, MR, Renedo, N et al.. Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment. Elife. 2017;6 :.
    doi: 10.7554/eLife.20420. PubMed PMID:28220755. PubMed Central PMC5319836.

  4. Huang, HL, Krieger, IV, Parai, MK, Gawandi, VB, Sacchettini, JC. Mycobacterium tuberculosis Malate Synthase Structures with Fragments Reveal a Portal for Substrate/Product Exchange. J. Biol. Chem. 2016;291 (53):27421-27432.
    doi: 10.1074/jbc.M116.750877. PubMed PMID:27738104. PubMed Central PMC5207166.

  5. Park, Y, Pacitto, A, Bayliss, T, Cleghorn, LA, Wang, Z, Hartman, T et al.. Essential but Not Vulnerable: Indazole Sulfonamides Targeting Inosine Monophosphate Dehydrogenase as Potential Leads against Mycobacterium tuberculosis. ACS Infect Dis. 2017;3 (1):18-33.
    doi: 10.1021/acsinfecdis.6b00103. PubMed PMID:27704782. .

  6. Palencia, A, Li, X, Bu, W, Choi, W, Ding, CZ, Easom, EE et al.. Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase. Antimicrob. Agents Chemother. 2016;60 (10):6271-80.
    doi: 10.1128/AAC.01339-16. PubMed PMID:27503647. PubMed Central PMC5038265.

  7. Martínez-Hoyos, M, Perez-Herran, E, Gulten, G, Encinas, L, Álvarez-Gómez, D, Alvarez, E et al.. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine. 2016;8 :291-301.
    doi: 10.1016/j.ebiom.2016.05.006. PubMed PMID:27428438. PubMed Central PMC4919555.

  8. Bhatt, VS, Zeng, D, Krieger, I, Sacchettini, JC, Cho, JH. Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl. Biophys. J. 2016;110 (12):2630-41.
    doi: 10.1016/j.bpj.2016.05.008. PubMed PMID:27332121. PubMed Central PMC4919510.

  9. Almeida, D, Ioerger, T, Tyagi, S, Li, SY, Mdluli, K, Andries, K et al.. Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2016;60 (8):4590-9.
    doi: 10.1128/AAC.00753-16. PubMed PMID:27185800. PubMed Central PMC4958187.

  10. Guardia, A, Gulten, G, Fernandez, R, Gómez, J, Wang, F, Convery, M et al.. N-Benzyl-4-((heteroaryl)methyl)benzamides: A New Class of Direct NADH-Dependent 2-trans Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity. ChemMedChem. 2016;11 (7):687-701.
    doi: 10.1002/cmdc.201600020. PubMed PMID:26934341. .

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