Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system.
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| Abstract |
The human kallikreins are a large multigene family of closely related serine-type proteases. In this regard, they are similar to the multigene kallikrein families characterized in mice and rats. There is a much more extensive body of knowledge regarding the function of mouse and rat kallikreins in comparison with the human kallikreins. Human kallikrein 6 has been proposed as the homologue to rat myelencephalon-specific protease, an arginine-specific degradative-type protease abundantly expressed in the central nervous system and implicated in demyelinating disease. We present the x-ray crystal structure of mature, active recombinant human kallikrein 6 at 1.75-A resolution. This high resolution model provides the first three-dimensional view of one of the human kallikreins and one of only a few structures of serine proteases predominantly expressed in the central nervous system. Enzymatic data are presented that support the identification of human kallikrein 6 as the functional homologue of rat myelencephalon-specific protease and are corroborated by a molecular phylogenetic analysis. Furthermore, the x-ray data provide support for the characterization of human kallikrein 6 as a degradative protease with structural features more similar to trypsin than the regulatory kallikreins.
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| Authors | Matthew J Bernett, Sachiko I Blaber, Isobel A Scarisbrick, Pushparani Dhanarajan, Steven M Thompson, Michael Blaber |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 27 Pg. 24562-70 (Jul 05 2002) ISSN: 0021-9258 [Print] United States |
| PMID | 11983703 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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