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J Biol Chem 2002 Apr 30
Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M.
Chemistry and Biochemistry, Florida State University, Tallahassee, Fl 32306-4380.
The human kallikreins are a large multi-gene family of closely-related serine-type proteases.
In this regard, they are similar to the multi-gene kallikrein families characterized in the mouse and rat.
There is a much more extensive body of knowledge regarding the function of mouse and rat kallikreins in comparison to 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 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 is presented that supports the identification of human kallikrein 6 as the functional homologue of rat myelencephalon specific protease and is corroborated by a molecular phylogenetic analysis.
Furthermore, the x-ray data provides support for the characterization of human kallikrein 6 as a degradative protease with structural features more similar to trypsin than the regulatory kallikreins.