Abstract

This project deals with the dissection and manipulation of protein structure. Alanine +RNA synthetase is to be used for these purposes. Fragments of the enzyme are to be produced in quantity and subjected to crystallization attempts. These fragments are know to encode specific functional domains. A major emphasis is placed on isolation and characterization of a small fragment that interacts with +RNA. Synthesis of polypeptides that encompass a putative +RNA binding domain will be attempted. Other studies focus on the manipulation of the alanine +RNA synthetase structure so as to achieve higher catalytic power and greater ligand affinities. Preliminary work has been done on a selected system for isolation of enzyme molecules with enhanced properties. This system will be explored for the isolation of protein in variants.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM037641-05
Application #
3856892
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Martinis, S A; Schimmel, P (1992) Enzymatic aminoacylation of sequence-specific RNA minihelices and hybrid duplexes with methionine. Proc Natl Acad Sci U S A 89:65-9
Miller, W T; Schimmel, P (1992) A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition. Proc Natl Acad Sci U S A 89:2032-5
Miller, W T; Hill, K A; Schimmel, P (1991) Evidence for a ""cysteine-histidine box"" metal-binding site in an Escherichia coli aminoacyl-tRNA synthetase. Biochemistry 30:6970-6
Kamradt, T; Soloway, P D; Perkins, D L et al. (1991) Pertussis toxin prevents the induction of peripheral T cell anergy and enhances the T cell response to an encephalitogenic peptide of myelin basic protein. J Immunol 147:3296-302
Musier-Forsyth, K; Usman, N; Scaringe, S et al. (1991) Specificity for aminoacylation of an RNA helix: an unpaired, exocyclic amino group in the minor groove. Science 253:784-6
Musier-Forsyth, K; Scaringe, S; Usman, N et al. (1991) Enzymatic aminoacylation of single-stranded RNA with an RNA cofactor. Proc Natl Acad Sci U S A 88:209-13
Toth, M J; Schimmel, P (1990) A mutation in the small (alpha) subunit of glycyl-tRNA synthetase affects amino acid activation and subunit association parameters. J Biol Chem 265:1005-9
Lai, M Z; Jang, Y J; Chen, L K et al. (1990) Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. J Immunol 144:4851-6
Park, S J; Miller, W T; Schimmel, P (1990) Synthetic peptide model of an essential region of an aminoacyl-tRNA synthetase. Biochemistry 29:9212-8
Toth, M J; Schimmel, P (1990) Deletions in the large (beta) subunit of a hetero-oligomeric aminoacyl-tRNA synthetase. J Biol Chem 265:1000-4

Showing the most recent 10 out of 17 publications