Molecular biology of tissue kallikrein

MacDonald, Raymond J.; Margolius, Harry S.; Erdös, Ervin G.

doi:10.1042/bj2530313

Cited by 156 publications

(68 citation statements)

References 129 publications

(132 reference statements)

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“…cipal known biological function is the highly selective hydrolysis of plasma high and low molecular mass kininogens at two different peptide bonds (Met 379 -Lys 380 and Arg 389 -Ser 390 ), with residues numbered on the basis of the structure of prekallikrein (3), to stoichiometrically release the vasoactive and spasmogenic decapeptide kallidin (Lysbradykinin) (2). Human tissue kallikrein (hK1) (4) also hydrolyzes various synthetic substrates such as Na-substituted arginine and lysine derivatives (amides, esters and fluorogenic peptides) (5-8), Cbz-Tyr-OpNP (9,10) and D-Pro-Phe-Phe-Nan (8).…”

Section: Mo Sousa Et Almentioning

confidence: 99%

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Linear competitive inhibition of human tissue kallikrein by 4-aminobenzamidine and benzamidine and linear mixed inhibition by 4-nitroaniline and aniline

Sousa

Miranda

Costa

et al. 2001

Braz J Med Biol Res

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Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide (7.5-90.0 µM) by human tissue kallikrein (hK1) (4.58-5.27 nM) at pH 9.0 and 37 o C was studied in the absence and in the presence of increasing concentrations of 4-aminobenzamidine (96-576 µM), benzamidine (1.27-7.62 mM), 4-nitroaniline (16.5-66 µM) and aniline (20-50 mM). The kinetic parameters determined in the absence of inhibitors were: K m = 12.0 ± 0.8 µM and k cat = 48.4 ± 1.0 min -1 . The data indicate that the inhibition of hK1 by 4-aminobenzamidine and benzamidine is linear competitive, while the inhibition by 4-nitroaniline and aniline is linear mixed, with the inhibitor being able to bind both to the free enzyme with a dissociation constant K i yielding an EI complex, and to the ES complex with a dissociation constant K i , yielding an ESI complex. The calculated K i values for 4-aminobenzamidine, benzamidine, 4-nitroaniline and aniline were 146 ± 10, 1,098 ± 91, 38.6 ± 5.2 and 37,340 ± 5,400 µM, respectively. The calculated K i values for 4-nitroaniline and aniline were 289.3 ± 92.8 and 310,500 ± 38,600 µM, respectively. The fact that K i >K i indicates that 4-nitroaniline and aniline bind to a second binding site in the enzyme with lower affinity than they bind to the active site. The data about the inhibition of hK1 by 4-aminobenzamidine and benzamidine help to explain previous observations that esters, anilides or chloromethyl ketone derivatives of Na-substituted arginine are more sensitive substrates or inhibitors of hK1 than the corresponding lysine compounds.

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Section: Mo Sousa Et Almentioning

confidence: 99%

“…The two groups differ in molecular weight, isoelectric point, substrate specificity, immunological characteristics, the type of kinin released, and functional importance (1). Tissue kallikreins are related to trypsin, but with a higher specificity for the cleavage site of polypeptide substrates (2). Their prin-…”

Section: Introductionmentioning

confidence: 99%

Linear competitive inhibition of human tissue kallikrein by 4-aminobenzamidine and benzamidine and linear mixed inhibition by 4-nitroaniline and aniline

Sousa

Miranda

Costa

et al. 2001

Braz J Med Biol Res

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“…The peptide bond connecting the propart to the active enzyme is the basic-to-hydrophobic amino acid link Arg-Ile, which can be cleaved in vitro by either trypsin-type enzymes or by enzymes with a cleavage specificity for hydrophobic residues at the N-terminus [2]. Tissue kallikreins, as other secretory proteins, are Although the steps involved in the enzyme activation of prokallikrein in vitro have been characterized, the intracellular DISCUSSION synthesized as inactive proenzymes with very short activation processing of the proenzyme is still undefined.…”

Section: Molecular and Functional Characterization Of Recombinant Promentioning

confidence: 99%

“…They share common biological features, especially the highly selective cleavage of the plasma protein kininogen to release the vasoactive and spasmogenic decapeptide kallidin (Lys-bradykinin) [2]. Tissue kallikreins are found in a variety of tissues like pancreas [3], salivary glands [4], kidney, intestine and prostate [5], but also in secretions of these tissues and different body fluids [6].…”

mentioning

confidence: 99%

Purification and characterization of human salivary‐gland prokallikrein from recombinant baculovirus‐infected insect cells

Angermann

Rahn

Hektor

et al. 1992

European Journal of Biochemistry

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A full-length cDNA encoding human salivary-gland preprokallikrein was inserted into the baculovirus Autogrupha calijornicu nuclear polyhedrosis virus downstream of the polyhedrin promoter. The gene was expressed in transfected Spodoptera,frugiperdu cells and the recombinant product secreted into the culture medium. By alternating anion-exchange chromatography and gel-filtration steps, twice repeated, prokallikrein was purified to homogeneity, which was confirmed by amino acid analysis and N-terminal sequence determination. The prepropeptide was processed correctly, including the removal of the signal peptide. The resulting proenzyme was found to be glycosylated, had a molecular mass of 35 kDa and an isoelectric point of 4.6. The yield of purified recombinant protein reached a level of 5 mg/l insect cell culture. After trypsin digestion of prokallikrein, the biological activity of the released kallikrein was demonstrated by its specific amidase, esterase and kininogenase activity. The expression and purification of prokallikrein, as described here, offers the opportunity to study the proenzyme activation through protein engineering techniques in detail.Human salivary-gland kallikrein is a member of the tissue or glandular kallikreins, which comprise a subfamily of trypsin-like serine proteinases of closely related structure with molecular masses between 25 -40 kDa due to the heterogeneity of their carbohydrate content [l]. They share common biological features, especially the highly selective cleavage of the plasma protein kininogen to release the vasoactive and spasmogenic decapeptide kallidin (Lys-bradykinin) [2]. Tissue kallikreins are found in a variety of tissues like pancreas [3], salivary glands [4], kidney, intestine and prostate [5], but also in secretions of these tissues and different body fluids [6].Comparison of full-length cDNA sequences of human salivary-gland kallikrein [7], pancreatic [8] and kidney [9] kallikrein, as well as the sequence of the kallikrein gene [lo], has shown that tissue kallikrein is synthesized as a precursor with a 17-amino-acid signal peptide and an activation peptide of seven amino acids in length with the sequence motif AlaPro-Pro-Ile-Gln-Ser-Arg (Fig. l), which is identical in all examined kallikrein species. The mature enzyme of 238 amino acids revealed a complete sequence identity with the exception of two amino acid exchanges in position 121 from Gln to Glu and position 162 from Glu to Lys in salivary-gland kallikrein. [12], kidney [13] and in urine, where both latent and active forms are found in equal amounts [14]. In contrast, in salivary tissue and secretions only the activated form occurs. As kallikrein is easily inhibited by various proteins and peptides [15], it was unknown whether an enhancement in kallikrein activity was due to the activation of the proenzyme or to the removal of an inhibitor. The establishment of isolation procedures for prokallikrein from porcine pancreas [16], human urine [17] and rat urine [18] allowed the investigation of the activation ...

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“…The kallikreins are found in glandular cells, neutrophils and biological fluids and can be divided into two main groups: plasma (EC 3.4.21.3 4) and tissue (EC 3.4.21.35) kallikreins 3 . The KLK1 gene, located on chromosome 19q13.4, expresses human tissue kallikrein (hK1) 4 , the principal known biochemical function of which is releasing the vasoactive and spasmogenic decapeptide kallidin (Lys-bradykinin) (Lys-BK) from the plasma protein lowmolecular-weigh kininogen 5 . The KLK1 gene expression is highest in the pancreas, kidney and salivary glands, but also in prostate, breast, testis, uterus, heart and central nervous system 4 .…”

Section: Introductionmentioning

confidence: 99%

Insuficiencia cardíaca

2005

Anales de Pediatría Continuada

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Molecular biology of tissue kallikrein

Abstract: Abbreviations used: a-and y-NGF, a and y subunits of the mouse nerve growth factor complex; EGF-BP, epidermal growth factor binding protein; mGK, designation for a mouse genomic kallikrein gene; NEP, neutral endopeptidase 24.

Cited by 156 publications

References 129 publications

Linear competitive inhibition of human tissue kallikrein by 4-aminobenzamidine and benzamidine and linear mixed inhibition by 4-nitroaniline and aniline

Linear competitive inhibition of human tissue kallikrein by 4-aminobenzamidine and benzamidine and linear mixed inhibition by 4-nitroaniline and aniline

Purification and characterization of human salivary‐gland prokallikrein from recombinant baculovirus‐infected insect cells

Insuficiencia cardíaca

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