2QXH

Crystal Structure of Human Kallikrein 7 in Complex with Suc-Ala-Ala-Pro-Phe-chloromethylketone

Summary for 2QXH

• Entry DOI: 10.2210/pdb2qxh/pdb
• Related: 2QXG 2QXI 2QXJ
• Descriptor: Kallikrein-7, N-(3-carboxypropanoyl)-L-alanyl-L-alanyl-N-[(2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl]-L-prolinamide (3 entities in total)
• Functional Keywords: 70-80 loop, active site inhibitor, chloromethyl ketone, alternative splicing, glycoprotein, hydrolase, protease, secreted, serine protease, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P49862
• Total number of polymer chains: 1
• Total formula weight: 25020.18

Authors

Debela, M.,Hess, P.,Magdolen, V.,Schechter, N.M.,Bode, W.,Goettig, P. (deposition date: 2007-08-11, release date: 2008-01-08, Last modification date: 2024-11-20)

Primary citation

Debela, M.,Hess, P.,Magdolen, V.,Schechter, N.M.,Steiner, T.,Huber, R.,Bode, W.,Goettig, P.
Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.
Proc.Natl.Acad.Sci.Usa, 104:16086-16091, 2007

PubMed Abstract: 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.

PubMed: 17909180
DOI: 10.1073/pnas.0707811104

Experimental method

X-RAY DIFFRACTION (2 Å)