SYNERGISTIC BINDING OF HYDROPHOBIC PROBES AND ZINC LIGANDS TO THERMOLYSIN

被引:6
作者
PFUETZNER, RA [1 ]
CHAN, WWC [1 ]
机构
[1] MCMASTER UNIV,DEPT BIOCHEM,HAMILTON L8N 3Z5,ONTARIO,CANADA
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1993年 / 218卷 / 02期
关键词
D O I
10.1111/j.1432-1033.1993.tb18405.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The strong synergism previously observed in the binding of inhibitors to two Zn-proteases, has also been found for thermolysin. As in earlier cases, the effects are produced by a small Zn-ligand (e.g. a hydroxamate) in the presence of another compound which contains the key structural features of specific substrates (a specificity probe). For thermolysin, the most effective specificity probes are hydrophobic derivatives of amines and amino acids (e.g. carbobenzyloxy-L-alaninol). Even the simple combination of benzyl alcohol and formohydroxamate displays considerable synergism. The above effects are temperature dependent and correlate well with a thermally induced conformational isomerization reported recently for this enzyme. Our results seem to be related to previous observations of substrate synergism in the reverse reaction and to superactivation by chemical modification of this enzyme. All these effects are consistent with a change in the environment of the catalytically important zinc atom upon binding of the hydrophobic side chain of the substrate. With the inclusion of thermolysin, binding synergism is now known to occur in an endopeptidase as well as in exopeptidases of diverse specificity. The general occurrence of this phenomenon in zinc proteases and its possible significance are discussed in an accompanying study.
引用
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页码:523 / 528
页数:6
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