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PDBsum entry 2jxd

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protein links
Hydrolase inhibitor PDB id
2jxd
Jmol
Contents
Protein chain
62 a.a. *
* Residue conservation analysis
PDB id:
2jxd
Name: Hydrolase inhibitor
Title: Nmr structure of human serine protease inhibitor kazal type ii (spink2)
Structure: Serine protease inhibitor kazal-type 2. Chain: a. Fragment: kazal-type domain. Synonym: acrosin-trypsin inhibitor, husi-ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: spink2. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 15 models
Authors: T.Chen,T.-R.Lee,P.-C.Lyu
Key ref:
T.Chen et al. (2009). Identification of trypsin-inhibitory site and structure determination of human SPINK2 serine proteinase inhibitor. Proteins, 77, 209-219. PubMed id: 19422058 DOI: 10.1002/prot.22432
Date:
15-Nov-07     Release date:   18-Nov-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20155  (ISK2_HUMAN) -  Serine protease inhibitor Kazal-type 2
Seq:
Struc:
84 a.a.
62 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     serine-type endopeptidase inhibitor activity     1 term  

 

 
DOI no: 10.1002/prot.22432 Proteins 77:209-219 (2009)
PubMed id: 19422058  
 
 
Identification of trypsin-inhibitory site and structure determination of human SPINK2 serine proteinase inhibitor.
T.Chen, T.R.Lee, W.G.Liang, W.S.Chang, P.C.Lyu.
 
  ABSTRACT  
 
Human serine proteinase inhibitor Kazal-type 2 (SPINK2) functions as a trypsin/acrosin inhibitor and is synthesized mainly in the testis and seminal vesicle where its activity is engaged in fertility. The SPINK2 protein contains a typical Kazal domain composed by six cysteine residues forming three disulfide bridges. The expression of SPINK2 is closely related to cancer such as lymphomas, in that a high transcript level of SPINK2 in patients with primary cutaneous follicle center cell lymphomas have better prognosis with lower mortality. To clarify the role of SPINK2 in cancer, we performed quantitative real-time PCR and showed that the expression level of SPINK2 is significantly elevated in most leukemia cell lines except B-lymphoblast TK-6 cells. The molecular function and structural features of SPINK2 were also investigated by employing the recombinant active and mutant inactive SPINK2 proteins to determine its key P2-P2' (Pro(23)-Arg(24)-His(25)-Phe(26)) active site. The inhibition assay results demonstrated that Arg(24) at the P1 site is crucial for the specificity of SPINK2 on target enzyme. Although His(25) at the P1' and Phe(26) at the P2' residues are also involved in trypsin-SPINK2 interaction, Pro(23) at the P2 site may not be directly participated in interacting with trypsin. In addition, we determined the 3D solution structure of SPINK2 and used this structure to predict the SPINK2-proteinase complex structure and binding properties. These studies not only provide critical information about the structural properties and biophysical features of the SPINK2 proteinase inhibitor, but also suggest its important role in tumor progression and response to treatment.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. The stereo view of rSPINK2 structure. The representative protein structure was generated by using PyMOL.[46] The well-defined portion of rSPINK2 stabilized by three disulfide bonds (colored in yellow sticks) comprises of a short three-stranded antiparallel -sheet (colored in cyan) and an -helix (colored in red). The loop regions are shown in green.
Figure 8.
Figure 8. The docking model of SPINK2 with trypsin. (A) The docked complex model, trypsinogen-SPINK2, was exhibited using Accelrys DS ViewerPro.[49] The P2-P2' residues were labeled as purple color. (B) Ser195, His57 and Asp102 (shown as green line) are catalytic triad of trypsin. The P2-P2' sites are shown as ball and stick. (C) PSTI and (D) SPINK2 interact with cow trypsin at the P2-P2' sites are represented by LIGPLOT diagrams.[43] The residues in trypsin were labeled as Z and inhibitors (PSTI or SPINK2) as I .
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2009, 77, 209-219) copyright 2009.  
  Figures were selected by an automated process.