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Literature summary for 3.4.21.117 extracted from

  • Debela, M.; Beaufort, N.; Magdolen, V.; Schechter, N.M.; Craik, C.S.; Schmitt, M.; Bode, W.; Goettig, P.
    Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7 (2008), Biol. Chem., 389, 623-632.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
analysis of crystal structure of KLK7: owing to the conformational restrictions of the relatively narrow S1 pocket, the formation of a stabilizing hydrogen bond between the P1-Tyr-OH and the carboxamide of Asn189 has to be mediated by a water molecule. The S2 subsite is less separated from the S4 subsite than in KLK4-6 and less limited in size owing to a different position of the His99 imidazole side chain, which may also contribute to the capacity for the adaptation to P2 side chains of various size Homo sapiens
two crystal structures of KLK7 are solved with either of two covalently bound chloromethyl ketone (CMK) inhibitors. Overall, the S1 pocket of KLK7 is larger and more hydrophobic than those of the tryptic KLK4, 5, and 6. The hydrophobicity of the S1 pocket is enhanced by the presence of Ala190 instead of Ser190, and at the bottom of the pocket, Asn189, a polar residue, replaces Asp189, a negatively charged residue. Consistent with specificity, Asn189 insteadof Asp189 would reduce the affinity of KLK7 for basic P1 side chains and allow binding of non-polar residues. The size and shape of the S1 pocket is well suited to accommodate residues with medium and large side chains, explaining the modified chymotryptic specificity. Tyr may be favored over Phe at P1 because of the potential of the carboxyamide group of Asn189 to hydrogen bond to a buried hydroxyl group Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Ala-Ala-Phe-chloromethylketone
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Homo sapiens
Suc-Ala-Ala-Pro-Phe-chloromethylketone
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Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell in contrast to the expression in ovarian cancer, high expression of KLK 7 is strongly associated with good prognosis in breast cancer patients Homo sapiens
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ovary cancer cell over-expressed in ovarian carcinoma tissues. Elevated KLK 7 mRNA expression in tumor tissue is associated with poorer prognosis for ovarian cancer patients Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acidic-sphingomyelinase + H2O
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Homo sapiens ?
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?
beta-glucocerebrosidase + H2O
-
Homo sapiens ?
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?
cathelicidin + H2O
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Homo sapiens ?
-
?
insulin beta chain + H2O the most preferred P1 residue of KLK7 is Tyr, followed by Ala and Met, whereas Phe, Arg, and Lys are ranked quite low. Tyr is favored at S2 over the medium-sized hydrophobic residues Leu, Thr, Met, and Phe. In agreement with these findings, KLK7 cleaves the insulin B-chain after Asn-Gln-His-Leu, Glu-Ala-Leu-Tyr, Gly-Phe-Phe-Tyr, and Arg-Gly-Phe-Phe Homo sapiens ?
-
?
additional information similar to KLK5, KLK7 degrades proteins of corneodesmosomes, which are most likely physiological substrates of KLKs expressed in the stratum corneum of skin Homo sapiens ?
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?

Synonyms

Synonyms Comment Organism
kallikrein 7
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Homo sapiens
KLK7
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Homo sapiens