H.F. Gilbert, Ph.D.
Professor, Biochemistry and Molecular Biology
Baylor College of Medicine
B.S. Chemistry, U. of Tennessee, Knoxville (1969)
Ph.D. Organic Chemistry, U. Wisconsin, Madison (1975)
William P. Jencks, Brandeis University (1975-1977)
The information that directs a newly synthesized protein to fold into its proper three-dimensional structure is contained within the primary sequence of the protein. Whereas, some proteins will spontaneously adopt their correct structures, there are some proteins that require the assistance of molecular chaperones and folding catalysts to fold rapidly and correctly. Reduced, denatured proteins often form large, insoluble aggregates in solution because the exposed hydrophobic residues associate promiscuously with each other. Understanding the mechanisms by which folding catalysts and chaperones facilitate correct folding is a challenging mechanistic and structural problem with obvious importance to the production of correctly folded recombinant proteins for therapeutic and research uses. Protein disulfide isomerase (PDI) is an abundant 57-kDa protein that resides in the lumen of the endoplasmic reticulum and catalyzes the formation and rearrangements of disulfide bonds in secreted proteins. PDI also serves as a molecular chaperone that can inhibit protein aggregation. Our studies are focusing on the structural basis of the biological and biochemical activities of this remarkable class of folding catalysts through mutagenesis and mechanistic approaches coupled to genetic and biochemical studies in S. cerevisiae.
- Yuan J, Cardenas AM, Gilbert HF and Palzkill T. Determination of the amino acid sequence requirements for catalysis by the highly proficient orotidine monophosphate decarboxylase. Protein Sci., 20(11):1891-906 (2011). PubMed
- Arredondo SA, Chen TF, Riggs AF, Gilbert HF and Georgiou G. Role of dimerization in the catalytic properties of the Escherichia coli disulfide isomerase DsbC. J Biol Chem, 284(36):23972-9 (2009). PubMed
- Kim JH, Zhao Y, Pan X, He X and Gilbert HF. The unfolded protein response is necessary but not sufficient to compensate for defects in disulfide isomerization. J Biol Chem, 284(16):10400-8 (2009). PubMed
- Arredondo S, Segatori L, Gilbert HF and Georgiou G. De novo design and evolution of artificial disulfide isomerase enzymes analogous to the bacterial DsbC. J Biol Chem, 283(46):31469-76 (2008). PubMed
- Samudio I, Konoplemva M, Hail N Jr, Shi YX, McQueen T, Hsu T, Evans R, Honda T, Gribble GW, Sporn M, Gilbert HF, Safe S and Andreeff M. 2-Cyano-3, 12-dioxooleana-1, 9-dien-28-imidazolide (CDDO-Im) directly targets mitondrial glutathione to induce apoptosis in pancreatic cancer. J Biol Chem, 280(43):36273-82 (2005). PubMed
- Xiao R, Lundström-Ljung J, Holmgren A and Gilbert HF. Catalysis of thiol/sulfide exchange. Gluaredoxin 1 and protein-disulfide isomerase use different mechanisms to enhance oxidase and reductase activities. J Biol Chem, 280(22):21099-106 (2005). PubMed
- Wilkinson B, Xiao R and Gilbert HF. A structural disulfide of yeast protein-disulfide isomerase destabilizes the active site disulfide of the N-terminal thioredoxin domain. J Biol Chem, 280(12):11483-7 (2005). PubMed
For more publications, see listing on PubMed.
Department: Biochemistry & Molecular Biology
Address: Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Additional Links: Biochemistry and Molecular Biology