The role of the D- and K-pathways of proton transfer in the function of the haem-copper oxidases

The X-ray structures of several haem-copper oxidases now at hand have given important constraints on how these enzymes function. Yet, dynamic data are required to elucidate the mechanisms of electron and proton transfer, the activation of O-2 and its reduction to water, as well as the still enigmati c mechanism by which these enzymes couple the redox reaction to proton tran slocation. Here, some recent observations will be briefly reviewed with spe cial emphasis on the functioning of the so-called D- and K-pathways of prot on transfer. It turns out that only one of the eight protons taken up by th e enzyme during its catalytic cycle is transferred via the K-pathway. The D -pathway is probably responsible for the transfer of all other protons, inc luding the four that are pumped across the membrane. The unique K-pathway p roton may be specifically required to aid O-O bond scission by the haem-cop per oxidases. (C) 2000 Elsevier Science B.V. All rights reserved.