Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal tissue kallikrein is a member of the multigene family of serine proteases called the tissue kallikrein (KLK) gene family. This is a highly conserved family of genes, with a genomic structural organization that is identical for all these genes and other genes in the larger serine protease family, such as trypsin and chymotrypsin. These genes exhibit high sequence similarity both within and between species. However, there are clearly areas of sequence variability, which is most apparent in regions that form the substrate binding pocket of each enzyme and confers the substrate specificity of each individual enzyme. These genes are also often expressed in the same tissue, although each gene can have an individual tissue-specific pattern of expression. Similar patterns of diversity yet identity are also apparent in the regulation of kallikrein gene expression or enzyme activity. These similarities, and the fact that several of these gene families are located in tight clusters in the genome, support the notion that they have arisen by gene duplication. In this review, an overview of the molecular biology of the renal tissue kallikrein (KLK1) gene and the larger KLK gene family is given, highlighting the similarities yet diversity that is the hallmark of this family of genes, and how this knowledge has, and will, impact on our understanding of the role these enzymes play in normal physiological events and disease.
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PMID:Current perspectives on the molecular biology of the renal tissue kallikrein gene and the related tissue kallikrein gene family. 983 May 2

We report the enzymatic properties and substrate specificity of human recombinant KLK3 in the presence of glycosaminoglycans (GAGs) and sodium citrate. This salt is highly concentrated in prostate and in its presence KLK3 had a similar hydrolytic efficiency as chymotrypsin. In contrast to the latter peptidase, KLK3 activated by sodium citrate efficiently hydrolyzed substrates containing R, H and P at the P1 position. Activated KLK3 also cleaved peptides derived from the bradykinin domain of human kininogen at the same sites as human kallikrein KLK1, but presented low kininogenase activity. Angiotensin I has several sites for hydrolysis by KLK3; however, it was cleaved only at the Y-I bond (DRVY downward arrowIHPFHL). Sodium citrate modulated KLK3 conformation as observed by alterations to the intrinsic fluorescence of phenylalanines and tryptophans. Activated KLK3 was reversibly inhibited by Z-Pro-Prolinal and competitively inhibited by ortho-phenantroline. Together, these are noteworthy observations for the future design of specific non-peptide inhibitors of KLK3 and to find natural substrates.
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PMID:Substrate specificity and inhibition of human kallikrein-related peptidase 3 (KLK3 or PSA) activated with sodium citrate and glycosaminoglycans. 2037 59