Refined 2 Å X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase

Bode, Wolfram; Chen, Zhongguo; Bartels, Klaus; Kutzbach, Carl; Schmidt-Kastner, G.; Bartunik, H.D.

doi:10.1016/0022-2836(83)90077-3

Cited by 230 publications

(133 citation statements)

References 56 publications

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“…The presence of an aspartate residue at position 182 indicates the trypsin-like specificity of the enzyme [23]. This result is in accord with the observed substrate specificity with synthetic substrates [8].…”

Section: Discussionsupporting

confidence: 79%

“…Also worthy of note is that Gly 205 and Ser 216 are present at homologous positions in canine prostatic arginine esterase as well as in human pancreatic kallikrein [16] and human PSA [6]. These amino acids are believed to allow access to the catalytic pocket of amino acid residues with bulky side chains [23]. Two other amino acids, Tyr 92 and Trp 204, are presumed to be important determinants for the hydrolysis of plasma kininogen and release of vasoactive kinins [24].…”

Section: Discussionmentioning

confidence: 99%

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Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

et al. 1988

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The nucleotide sequence of canine prostate arginine esterase mRNA was determined using a 400 bp cDNA clone and primer-extended cDNA transcripts for the 5'coding and noncoding regions. The mRNA contains 864 nucleotides encoding a protein of 236 amino acids preceded by 24 amino acids which constitutes both the signal and the zymogen peptides. The sequence indicates the presence of one potential glycosylation site. A high degree of homology was found between the canine enzyme and other members of the kallikrein family including human prostate specific antigen. The protein appears to be specified by a single gene.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

et al. 1988

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“…Unlike most of the former, but similarly to the latter, pro-hK6 lacks the kallikrein loop (see below and Fig. 1), important for kallikrein specificity and a point at which the polypeptide is cleaved and where an N-glycosylation site is located in kallikrein A, kallikrein-13, and other family members although not in pro-hK6 (67). However, only 3 of the 15 human kallikreins have the complete loop, believed to confer specificity for kininogenase activity (5).…”

Section: Resultsmentioning

confidence: 99%

The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family

Gomis‐Rüth¹,

Bayés²,

Sotiropoulou³

et al. 2002

Journal of Biological Chemistry

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Zyme/protease M/neurosin/human kallikrein 6 (hK6) is a member of the human kallikrein family of trypsinlike serine proteinases and was originally identified as being down-regulated in metastatic breast and ovarian tumors when compared with corresponding primary tumors. Recent evidence suggests that hK6 may serve as a circulating tumor marker in ovarian cancers. In addition, it was described in the brain of Parkinson's disease and Alzheimer's disease patients, where it is implicated in amyloid precursor protein processing. It is thus a biomarker for these diseases. To examine the mechanism of activation of hK6, we have solved the structure of its proform, the first of a human kallikrein family member. The proenzyme displays a fold that exhibits chimeric features between those of trypsinogen and other family members. It lacks the characteristic "kallikrein loop" and forms the six disulfide bridges of trypsin. Pro-hK6 displays a completely closed specificity pocket and a unique conformation of the regions involved in structural rearrangements upon proteolytic cleavage activation. This points to a novel activation mechanism, which could be extrapolated to other human kallikreins.

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“…The sequences of murine y-NGF (Thomas et al, 1981a;Ullrich et al, 1984). a-NGF , and EGF-BP (Blaber et al, 1987;Drinkwater et al, 1987;Isackson et al, 1987b) are shown aligned with the sequences of rat tonin (Lazure et al, 1984;Ashley & MacDonald, 1985) and PPK (Tschesche et al, 1979;Bode et al, 1983). Residues absent from the mature form of y-NGF (and EGF-BP) are indicated by lowercase letters.…”

Section: Loop 2: Residues 56-64mentioning

confidence: 99%

“…This loop has been called the kallikrein loop because of the characteristically long insertion in this loop compared with other serine proteases. In tonin, residues 95C-95J are not visible in the final electron density map (Fujinaga & James, 1987), whereas in PPK this loop also appears disordered and contains an internal cleavage site (see Bode et al, 1983). Comparison of the amino acid sequence (Thomas et al, 1981a) of y-NGF with the sequence derived from a cDNA showed that a four-residue peptide is cleaved from the mature form of y-NGF (see Fig.…”

Section: Loop 2: Residues 56-64mentioning

confidence: 99%

Prediction of the three‐dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein

et al. 1993

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We have predicted the three‐dimensional structures of the serine protease subunits (γ‐NGF, α‐NGF, and EGF‐BP) of the high molecular weight complexes of nerve growth factor (7S NGF) and epidermal growth factor (HMW‐EGF) from the mouse submandibular gland (from the X‐ray crystal structures of two related glandular kallikreins). The conformations of three of the six loops surrounding the active site are relatively well defined in the models of γ‐NGF and EGF‐BP, but three other loops are likely to have flexible conformations. Although the amino acid sequence of α‐NGF is closely related to those of γ‐NGF and EGF‐BP, it is catalytically inactive. Model‐building studies on α‐NGF suggested that mutations (in α‐NGF) just prior to the active site serine (195) and an unusual N‐terminal sequence are consistent with α‐NGF having a zymogen‐like conformation (similar to that in chymotrypsinogen). An hypothetical model of the quaternary structure of HMW‐EGF has been constructed using this model of EGF‐BP and the NMR structure of murine EGF. The C‐terminal arm of EGF was modeled into the active site of EGF‐BP based on data indicating that the C‐terminal arginine of EGF occupies the S1 subsite of EGF‐BP. Data suggesting one of the surface loops of EGF‐BP is buried in the HMW‐EGF complex and symmetry constraints were important in deriving a schematic model. A molecular docking program was used to fit EGF to EGF‐BP.

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Refined 2 Å X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase

Cited by 230 publications

References 56 publications

Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

Nucleotide sequence of the androgen‐dependent arginine esterase mRNA of canine prostate

The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family

Prediction of the three‐dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein

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