Abstract

1. Biochemistry of Protein Isoprenylation. It has recently been shown that a product(s) derived from mevalonic acid becomes attached to proteins in animal cells. The role of this novel post-translational lipidation will be probed. The chemical structure of the lipid, its mode of attachment to proteins and the enzymology of the modification will be studied. 2. Enzymology of Phospholipase A2. We will continue to study the inhibition of phospholipase A2 using carefully constructed assay systems. The inhibition by lipocortins, analogs of manoalide, and lysocardiolipins will be studied in detail. 3. Inhibition of Diaminopimelic Acid Epimerase. Beta-fluorinated analogs of diaminopimelic acid are potent inhibitors of bacterial diaminopimelic acid. The mechanism of the inhibition will be studied in detail.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Modified Research Career Development Award (K04)
Project #
5K04GM000562-02
Application #
3072947
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Liu, L; Jang, G F; Farnsworth, C C et al. (1995) Synthetic prenylated peptides: studying prenyl protein-specific endoprotease and other aspects of protein prenylation. Methods Enzymol 250:189-206
Jang, G F; Yokoyama, K; Gelb, M H (1993) A prenylated protein-specific endoprotease in rat liver microsomes that produces a carboxyl-terminal tripeptide. Biochemistry 32:9500-7
Bayburt, T; Yu, B Z; Lin, H K et al. (1993) Human nonpancreatic secreted phospholipase A2: interfacial parameters, substrate specificities, and competitive inhibitors. Biochemistry 32:573-82
James, M N; Sielecki, A R; Hayakawa, K et al. (1992) Crystallographic analysis of transition state mimics bound to penicillopepsin: difluorostatine- and difluorostatone-containing peptides. Biochemistry 31:3872-86
Ghomashchi, F; Schuttel, S; Jain, M K et al. (1992) Kinetic analysis of a high molecular weight phospholipase A2 from rat kidney: divalent metal-dependent trapping of enzyme on product-containing vesicles. Biochemistry 31:3814-24
Yokoyama, K; Goodwin, G W; Ghomashchi, F et al. (1992) Protein prenyltransferases. Biochem Soc Trans 20:489-94
Ghomashchi, F; Yu, B Z; Mihelich, E D et al. (1991) Kinetic characterization of phospholipase A2 modified by manoalogue. Biochemistry 30:9559-69
Farnsworth, C C; Kawata, M; Yoshida, Y et al. (1991) C terminus of the small GTP-binding protein smg p25A contains two geranylgeranylated cysteine residues and a methyl ester. Proc Natl Acad Sci U S A 88:6196-200
Yokoyama, K; Goodwin, G W; Ghomashchi, F et al. (1991) A protein geranylgeranyltransferase from bovine brain: implications for protein prenylation specificity. Proc Natl Acad Sci U S A 88:5302-6
Kawata, M; Farnsworth, C C; Yoshida, Y et al. (1990) Posttranslationally processed structure of the human platelet protein smg p21B: evidence for geranylgeranylation and carboxyl methylation of the C-terminal cysteine. Proc Natl Acad Sci U S A 87:8960-4