Kazal-type inhibitors

Canonical mechanism kunitz- and kazal-type inhibitors... 

We demonstrate the latter approaeh on a small protein domain, which is homologous to proteins that are present in the protein data bank [86], As can be nicely seen in Fig. 55, rhodniin, which is homologous to other Kazal-type inhibitors, is found in the protein data bank. Here, the sequence homology is quite high. However, also structures with almost no sequence homologies are detected, as is the case for dihydrofolate reductase and D-xylose isomerase. 

KAZAL Kazal type serine protease inhibitors E(M) 0(0) 3(26) 1AN1... 

Kazal-type 5 (SPINK5), also known as LEKT1 [212-214], It is likely that inactivation of the inhibitor leads to overactivity of hK5, hK7, and possibly other kallikreins in skin. The same general mechanism may apply to psoriasis (our unpublished data). Clearly, a possible kallikrein cascade in skin, including active enzymes and inhibitors, needs to be further investigated. 

Serpins consist of a conserved core of three P-sheets and eight or nine a-helices that act collectively in the inhibitory mechanism. As with the Kazal- and Kunitz-type inhibitors, the mechanism involves a surface exposed loop that is termed the reactive center loop (RCL). The RCL presents a short stretch of polypeptide sequence bearing the Pl-Pl scissile bond. Like other serine protease inhibitor families, the PI residue dominates the thermodynamics that govern the interaction between protease and inhibitor. Exposure of the PI residue to solvent is typically brokered by 15 amino acids N-terminal to the PI residue and 5 residues on the C-terminal prime side of the scissile bond. Evidence for dramatic conformational change in the inhibitory mechanism was first provided by the crystal structure of the cleaved form of ai-antitrypsin (37). In this structure and unlike the native form, the reactive center loop was not solvent exposed but occurred as an additional P-strand within the core of the structure. 

Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, Landt O, Becker M. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat. Genet. 2000 25 213-216. 

There appears to be sequence homology between the pineapple stem bromelain inhibitors and some of the small molecular weight inhibitors from the legumlnosae (91) Human inter-a-trypsin inhibitor contains two domains with great similarity to the domains of the Kunitz-type inhibitors (44 92-94)> The ovoinhibitors from Japanese quail and chicken egg whites contain six tandem domains which are homologous to the Kazal pancreatic secretory inhibitor and to the ovomucoids (69) ... 

Vasotab, a vasoactive 56-peptide from horse fly Hybomitra bimaculata (Diptera, Taban-idae) salivary glands. The peptide contains six cysteine residues which form three disulfide bonds similar to the disulfide pattern of the Kazal-type protease inhibitors. In comparison to the latter, vasotab has an unique 7-amino-acid insertion between the third and fourth cysteine residues within the peptide chain. Vasotab shows positive inotropism in isolated rat hearts, vasodilatation of coronary and peripheral vessels, and Na+/K+-ATPase inhibition. Furthermore, it is capable of blocking L-type calcium channels [P. Takac et al., J. Exp. Biol. 2006, 209, 343]. 

Nirmala, X., Kodrik, D., Zurovec, M. and Sehnal, F. (2001), Insect silk contains both a Kunitz-type and a unique Kazal-type proteinase inhibitor , Eur. J. Biochem. 

Kazal family inhibitors - the type of trypsin inhibitor-like proteinase, commonly found in animals, including invertebrates. Molecules consist of one or more domains, and three disulfide bridges. The sequence of many often conservative, but the site of binding to the enzyme can be variable (Li et al., 2009 Rimphanitchayakit Tassanakajon, 2010) Kazal inhibitors are involved in various pathologies of the pancreas. In particular inhibitor Kazal SPINKl is expressed not only in normal cells of the pancreas, but also transformed. It is... 

Molecular cloning and expression of a novel Kazal-type serine proteinase inhibitor gene from Zhikong scallop Chlamys farreri, and the inhibitory activity of its recombinant domain. Fish Shellfish Immunol, 24, 629-637. 

The Streptomyces subtilisin inhibitor is closely related to the Kazal inhibitor family (Laskowski and Kato, 1980). The subunits of this dimeric inhibitor dissociate during thermal unfolding (Takahashi and Sturtevant, 1981), when dilute solutions (2--5 mg/ml) are heated slowly (l C/min) in a Privalov (1980) type of DSC instrument. The Td for Strepton yces subtilisin inhibitor is 17 C above that for STI at this heating rate (Table II), suggesting that it is intermediate in stability among the inhibitors tested. 

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