2qxi: Difference between revisions

Revision as of 19:43, 21 February 2008

High resolution structure of Human Kallikrein 7 in Complex with Suc-Ala-Ala-Pro-Phe-chloromethylketone

OverviewOverview

hK7 or human stratum corneum chymotryptic enzyme belongs to the human tissue kallikrein (hKs) serine proteinase family and is strongly expressed in the upper layers of the epidermis. It participates in skin desquamation but is also implicated in diverse skin diseases and is a potential biomarker of ovarian cancer. We have solved x-ray structures of recombinant active hK7 at medium and atomic resolution in the presence of the inhibitors succinyl-Ala-Ala-Pro-Phe-chloromethyl ketone and Ala-Ala-Phe-chloromethyl ketone. The most distinguishing features of hK7 are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr residues, as shown by kinetic data. Similar to several other kallikreins, the enzyme activity is inhibited by Zn(2+) and Cu(2+) at low micromolar concentrations. Biochemical analyses of the mutants H99A and H41F confirm that only the metal-binding site at His(99) close to the catalytic triad accounts for the noncompetitive Zn(2+) inhibition type. Additionally, hK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition.

About this StructureAbout this Structure

2QXI is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Stratum corneum chymotryptic enzyme, with EC number 3.4.21.117 Full crystallographic information is available from OCA.

ReferenceReference

Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7., Debela M, Hess P, Magdolen V, Schechter NM, Steiner T, Huber R, Bode W, Goettig P, Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16086-91. Epub 2007 Oct 1. PMID:17909180

Page seeded by OCA on Thu Feb 21 18:43:05 2008

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OCA

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 ==Overview==
-hK7 or human stratum corneum chymotryptic enzyme belongs to the human, tissue kallikrein (hKs) serine proteinase family and is strongly expressed, in the upper layers of the epidermis. It participates in skin desquamation, but is also implicated in diverse skin diseases and is a potential, biomarker of ovarian cancer. We have solved x-ray structures of, recombinant active hK7 at medium and atomic resolution in the presence of, the inhibitors succinyl-Ala-Ala-Pro-Phe-chloromethyl ketone and, Ala-Ala-Phe-chloromethyl ketone. The most distinguishing features of hK7, are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr, residues, as shown by kinetic data. Similar to several other kallikreins, the enzyme activity is inhibited by Zn(2+) and Cu(2+) at low micromolar, concentrations. Biochemical analyses of the mutants H99A and H41F confirm, that only the metal-binding site at His(99) close to the catalytic triad, accounts for the noncompetitive Zn(2+) inhibition type. Additionally, hK7, exhibits large positively charged surface patches, representing putative, exosites for prime side substrate recognition.
+hK7 or human stratum corneum chymotryptic enzyme belongs to the human tissue kallikrein (hKs) serine proteinase family and is strongly expressed in the upper layers of the epidermis. It participates in skin desquamation but is also implicated in diverse skin diseases and is a potential biomarker of ovarian cancer. We have solved x-ray structures of recombinant active hK7 at medium and atomic resolution in the presence of the inhibitors succinyl-Ala-Ala-Pro-Phe-chloromethyl ketone and Ala-Ala-Phe-chloromethyl ketone. The most distinguishing features of hK7 are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr residues, as shown by kinetic data. Similar to several other kallikreins, the enzyme activity is inhibited by Zn(2+) and Cu(2+) at low micromolar concentrations. Biochemical analyses of the mutants H99A and H41F confirm that only the metal-binding site at His(99) close to the catalytic triad accounts for the noncompetitive Zn(2+) inhibition type. Additionally, hK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition.
 ==About this Structure==
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 [[Category: Hess, P.]]
 [[Category: Magdolen, V.]]
-[[Category: Schechter, N.M.]]
+[[Category: Schechter, N M.]]
 [[Category: K7J]]
 [[Category: alternate conformations]]
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 [[Category: zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:15:43 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:43:05 2008''