11 



Some studies on the structure and 

 activity of papain* 



EMILL. SMITH, ROBERT L.HILL 

 AND J. R.KIMMEL 



The Laboratory for the Study of Hereditary and Metabolic Disorders and the 



Departments of Biological Chemistry and Medicine, University of Utah College 



of Medicine, Salt Lake City, Utah 



The successful elucidation of the structure of insulins from several species, 

 and of a number of smaller polypeptide hormones and antibiotics has 

 stimulated efforts to understand the relationship between protein structure 

 and biological activity.^ Enzymes are particularly suited for such investiga- 

 tion inasmuch as their activity and specificity can be studied in vitro. The 

 structure of several enzymes is now^ being investigated in a number of 

 laboratories, and it is likely that these efforts will soon be successfully com- 

 pleted in the case of a few of the smaller molecules. However, a knowledge 

 of amino acid sequence will not by itself solve the problem of correlating 

 structure and function. Much more information will be necessary to achieve 

 real understanding of the catalytic properties of enzymes. First of all, the 

 region or regions of the protein which are involved in specific interaction 

 with the substrates must be identified and a satisfactory explanation of the 

 substrate specificity must be at hand. Secondly, the kinetic behavior and 

 overall reaction mechanism must be expHcable in terms of the enzyme struc- 

 ture. It is obviously a difficult task at present to find enzymes of suitable 

 purity and availability which lend themselves to all of the necessary types 

 of study and which are small enough to permit attacking the problem of 

 structure by presently available methods. 



In our laboratory, we have chosen a proteolytic enzyme, papain, for in- 

 tensive study because it possesses a number of desirable features ; however, 

 it has some disadvantages as well. Among the many advantages which 

 papain possesses is the fact that the enzyme can be readily isolated in reason- 

 able quantity from the commercially available dried papaya latex. ^ As with 



* The work reported has been supported in large part by grants from the National 

 Institutes of Health, United States Public Health Service, The American Cancer Society 

 and the Rockefeller Foundation. 



