Calmodulin is an intracellular Ca++binding protein that is known to regulate the activities of a number of different enzymes in a Ca++-dependent manner. Many of these calmodulin-dependent enzymes are known to have significant biochemical roles in the function of various tissues of the cardiopulmonary system. However, little is presently known at the molecular level about the interactions of calmodulin with its target enzymes. The amino acid sequence of the calmodulin-binding domain of one well-studied calmodulin-dependent enzyme, myosin light chain kinase (MLCK), has recently been determined and synthetic peptides corresponding to this sequence have been prepared. These MLCK calmodulin-binding peptides appear to interact with calmodulin in much the same way as the native protein and are therefore useful models for studying calmodulin-- target enzyme interactions at the molecular level. The purpose of the proposed research is to develop a library of synthetic MLCK peptides containing an assortment of different molecular probes at specific positions within the peptide sequence. This library of labeled peptides will be used to characterize peptide-calmodulin interactions in some detail. These studies can be extended to other calmodulin-dependent enzymes and should provide a basis for understanding the mechanisms of calmodulin-regulated processes. It is conceivable that the information gained from these studies will be useful in developing therapeutic agents that could be used in the treatment of diseases such as hypertension and asthma where calmodulin-regulated processes are known to be involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM039290-02
Application #
3466663
Study Section
Biochemistry Study Section (BIO)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Health Center at Tyler
Department
Type
Hospitals
DUNS #
City
Tyler
State
TX
Country
United States
Zip Code
75708