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Hiram F Gilbert
Baylor College of MedicineDepartment: Biochemistry & Molecular BiologyAddress: Baylor College of Medicine One Baylor Plaza Houston, TX 77030 Phone: 713-798-4032 Fax: 713-798-6325 Email: hgilbert@bcm.tmc.edu Web: www.bcm.edu/biochem/?PMID=3763 |
Education
B.S. Chemistry, U. of Tennessee, Knoxville (1969)
Ph.D. Organic Chemistry, U. Wisconsin, Madison (1975)
William P. Jencks, Brandeis University (1975-1977)
Honors
Research Career Development Award, National Institutes of Health, 1982-1986
Research Topic
Protein folding and catalysis of disulfide formation during protein secretion in yeast
Research Description
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.
Selected Publications
- Xiao, Ruoyu, Lundström-Ljung, Johanna, Holmgren, Arne Gilbert, Hiram F. (2005) Catalysis of Thiol/Disulfide Exchange: Glutaredoxin 1 and Protien-Disulfide Isomerase use different mechanisms to enhance oxidase and reductase activities. J. Biol. Chem. 280: 21099 - 21106 278: 7154-7159.
- Wilkinson, B., Xiao, R., and Gilbert, H. F. (2005) Structural Disulfide of yeast protein disulfide isomerase destabilizes the active site disulfide of the N-terminal thioredoxin domain. (J. Biol. Chem. 280: 11483 - 11487)
- Xiao, R., Wilkinson, B., Solovyov, A., Lundstron-Ljung, J., Wijther, J. R., Holmgren, A., and Gilbert, H. F. (2004) Protein disulfide isomerase is an oxidase and isomerase in the S. cerevisiae endoplasmic reticulum. J. Biol. Chem. 279: 49780-49786
- Segatori, L., Paukstelis P.J., Gilbert, H. F., Georgiou, G (2004) Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways. Proc Natl Acad Sci U S A. 101: 10018-23.
- Wilkinson, B., and Gilbert, H. F. (2004) Protein disulfide isomerase. Biochem. Biophy. Acta 1699, 35-44
- Solovyov, A., *Xiao, R., and Gilbert, H. F. (2004) Sulfhydryl oxidation, not disulfide isomerization is the principal function of protein disulfide isomerase in yeast S. cerevisiae. J. Biol. Chem. 279: 34095 - 34100
- Gilbert, H. F. (2004) Disulfide bond formation, in Encyclopedia of Biological Chemistry, (W. J. Lennarz and M. D. Lane, eds), Elsevier, Oxford, Vol. 1, 598-602.
- Solovyov, A., and Gilbert, H. F. (2004) Zinc-dependent dimerization of the folding catalyst, protein disulfide isomerase. Prot. Sci. 13, 1902-1907
- Schwaller, M. F., Wilkinson, B. and Gilbert, H. F. (2003) Reduction/reoxidation cycles contribute to catalysis of disulfide isomerization by protein disulfide isomerase. J. Biol. Chem. 278, 7154-7159
Lab Members
Current Graduate Students
Former Grad Students
Current Post Docs
Former Post Docs
Lab Photos
Last edited on: September 21, 2009