Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system.
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.
Bernett
Matthew J
MJ
Institute of Molecular Biophysics, Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4380, USA.
Blaber
Sachiko I
SI
Scarisbrick
Isobel A
IA
Dhanarajan
Pushparani
P
Thompson
Steven M
SM
Blaber
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000201:enzymology*; D016384:Consensus Sequence; D006801:Humans; D007610:Kallikreins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism
C103551:KLK6 protein, human; D007610:Kallikreins; C491223:Prss18 protein, mouse; D014357:Trypsin