PDBsum entry 2qxj

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Hydrolase PDB id
Protein chain
224 a.a. *
_CU ×2
Waters ×86
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of human kallikrein 7 in complex with suc- ala-ala-pro-phe-chloromethylketone and copper
Structure: Kallikrein-7. Chain: a. Synonym: hk7, stratum corneum chymotryptic enzyme, hscce, serine protease 6. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: klk7, prss6, scce. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
2.10Å     R-factor:   0.214     R-free:   0.248
Authors: M.Debela,P.Hess,V.Magdolen,N.M.Schechter,W.Bode,P.Goettig
Key ref:
M.Debela et al. (2007). Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7. Proc Natl Acad Sci U S A, 104, 16086-16091. PubMed id: 17909180 DOI: 10.1073/pnas.0707811104
11-Aug-07     Release date:   08-Jan-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P49862  (KLK7_HUMAN) -  Kallikrein-7
253 a.a.
224 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Stratum corneum chymotryptic enzyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     extracellular matrix organization   4 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1073/pnas.0707811104 Proc Natl Acad Sci U S A 104:16086-16091 (2007)
PubMed id: 17909180  
Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.
M.Debela, P.Hess, V.Magdolen, N.M.Schechter, T.Steiner, R.Huber, W.Bode, P.Goettig.
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.
  Selected figure(s)  
Figure 4.
Fig. 4. Stick model of the modeled substrate Glu-Ala-Leu-Tyr-Leu-Val, the catalytic triad and the backbone of Gly^193, Ser^195, and Gly^216 of hK7[I] in stereo, including hydrogen bonds as dotted lines. The S1 pocket is depicted as transparent green surface according to volume calculations with VOIDOO (41). The specificity for P1 Tyr is most likely conferred by Asn^189 via hydrogen bonds from the carboxamide side chain to an interconnecting water molecule and to the Tyr OH group, respectively.
Figure 5.
Fig. 5. The copper ions bound at His^99 and His^41 displayed as blue spheres surrounded by electron density of the anomalous Fourier map in red (contour 5 ) in stereo. His^57 has the capacity for liganding Cu1 and Cu2 by a side chain rotation (His57*), requiring shifts of the ions, whereas the mutant H99A proves that only the His^99 site is the structural basis for the Zn^2+ and Cu^2+ inhibition of hK7.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21424930 A.Ishida-Yamamoto, and M.Kishibe (2011).
Involvement of corneodesmosome degradation and lamellar granule transportation in the desquamation process.
  Med Mol Morphol, 44, 1-6.  
21543845 A.Sukhwal, M.Bhattacharyya, and S.Vishveshwara (2011).
Network approach for capturing ligand-induced subtle global changes in protein structures.
  Acta Crystallogr D Biol Crystallogr, 67, 429-439.  
  20665732 H.Zhao, Y.Dong, J.Quan, R.Smith, A.Lam, S.Weinstein, J.Clements, N.W.Johnson, and J.Gao (2011).
Correlation of the expression of human kallikrein-related peptidases 4 and 7 with the prognosis in oral squamous cell carcinoma.
  Head Neck, 33, 566-572.  
20180638 J.E.Swedberg, Veer, and J.M.Harris (2010).
Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia.
  Biol Chem, 391, 357-374.  
20615447 P.Goettig, V.Magdolen, and H.Brandstetter (2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
  Biochimie, 92, 1546-1567.  
18844454 J.A.Clements (2008).
Reflections on the tissue kallikrein and kallikrein-related peptidase family - from mice to men - what have we learnt in the last two decades?
  Biol Chem, 389, 1447-1454.  
18627343 M.Debela, N.Beaufort, V.Magdolen, N.M.Schechter, C.S.Craik, M.Schmitt, W.Bode, and P.Goettig (2008).
Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7.
  Biol Chem, 389, 623-632.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.