422 2. ANALOGS OF ENZYME REACTION COMPONENTS 



binding since alteration of the positions, as in a-methylmannoside or a- 

 methylgalactoside, abolishes the inhibition, and omission, as in a-methyl- 

 xyloside, also prevents binding. The substitution of a methyl group on C-1 

 of ring B (/?-methylmaltoside) does not interfere with the binding, since 

 this analog has approximately the same affinity for the enzyme as the sub- 

 strate maltose. Alteration of the glycosidic link from the o;-l,4 in maltose 

 to the /?-l,4 in cellobiose does not result in an inhibitor, and other changes 

 (as in trehalose, sucrose, dextran, or lactose) likewise reduce the affinity. 

 The requirements for binding may be summarized as (1) a glucose-like con- 

 figuration of hydroxyl groups in ring A, (2) a glycosidic link of the a- 1,4 

 type, and (3) a widely variable glycosidic group. 



An a-mannosidase of Streptomyces griseus with a-phenylmannoside as the 

 substrate is inhibited competitively (probably) by several sugars and gly- 

 cosides (Hockenhull et al., 1954 c) and the relative binding energies have 

 been estimated on this basis (see tabulation), although the reliability of 



these figures is quite low due to variations between experiments. The man- 

 nose configuration seems to confer strong binding, as expected, but the high 

 inhibitory activities of maltose and cellobiose {a and /5 glucosides, respec- 

 tively), especially in view of the weak inhibitions produced by a-methyl- 

 glucoside and glucose, are unexpected and perhaps indicate that these sub- 

 stances are oriented on the enzyme surface in a different way than the 

 substrate, although there is no necessity to postulate an irreversible com- 

 plex as did Hockenhull and his co-workers. The active centers for such 

 enzymes probably possess several binding groups for the hydroxyls arrang- 

 ed in a certain pattern; glycosides other than the substrate could conceivably 



