PDBsum entry 1pxv

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Hydrolase PDB id
Protein chains
183 a.a.
111 a.a.
SO4 ×5
Waters ×458
PDB id:
Name: Hydrolase
Title: The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease
Structure: Cysteine protease. Chain: a, b. Engineered: yes. Mutation: yes. Cysteine protease inhibitor. Chain: c, d. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: staphopain b. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: staphostatin b.
Biol. unit: Dimer (from PQS)
1.80Å     R-factor:   0.192     R-free:   0.221
Authors: R.Filipek,M.Rzychon,A.Oleksy,M.Gruca,A.Dubin,J.Potempa, M.Bochtler
Key ref:
R.Filipek et al. (2003). The Staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease. J Biol Chem, 278, 40959-40966. PubMed id: 12874290 DOI: 10.1074/jbc.M302926200
07-Jul-03     Release date:   21-Oct-03    
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Protein chains
Pfam   ArchSchema ?
P0C1S6  (SSPB_STAAU) -  Staphopain B
393 a.a.
183 a.a.*
Protein chains
Pfam   ArchSchema ?
Q9EYW6  (SSPC_STAA8) -  Staphostatin B
109 a.a.
111 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 11 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     pathogenesis   4 terms 
  Biochemical function     peptidase inhibitor activity     4 terms  


DOI no: 10.1074/jbc.M302926200 J Biol Chem 278:40959-40966 (2003)
PubMed id: 12874290  
The Staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease.
R.Filipek, M.Rzychon, A.Oleksy, M.Gruca, A.Dubin, J.Potempa, M.Bochtler.
Staphostatins are the endogenous inhibitors of the major secreted cysteine proteases of Staphylococcus aureus, the staphopains. Our recent crystal structure of staphostatin B has shown that this inhibitor forms a mixed, eight-stranded beta-barrel with statistically significant similarity to lipocalins, but not to cystatins. We now present the 1.8-A crystal structure of staphostatin B in complex with an inactive mutant of its target protease. The complex is held together through extensive interactions and buries a total surface area of 2300 A2. Unexpectedly for a cysteine protease inhibitor, staphostatin B binds to staphopain B in an almost substrate-like manner. The inhibitor polypeptide chain runs through the protease active site cleft in the forward direction, with residues IG-TS in P2 to P2' positions. Both in the free and complexed forms, the P1 glycine residue of the inhibitor is in a main chain conformation only accessible to glycines. Mutations in this residue lead to a loss of affinity of the inhibitor for protease and convert the inhibitor into a substrate.
  Selected figure(s)  
Figure 2.
FIG. 2. Stereo C traces of the staphopain B-staphostatin B complex (A) and of the papain-human stefin B complex (1STF [PDB] ) as described in Ref. 30 (B). The coloring is consistent with Fig. 1, but the orientation is different. Every tenth residue is again marked with a ball. Protease with chain ID A and inhibitor with chain ID C were used for the figure.
Figure 4.
FIG. 4. Gel filtration profiles for wild-type (wt) inhibitor and the P1 glycine to alanine and glycine to arginine mutants. The dotted trace (dark gray) is obtained if only the inactive alanine mutant of protease is injected. The continuous trace (black) shows the result of injecting inhibitor only. The dot-dashed trace (light gray) shows the migration behavior if protease and inhibitor are coinjected.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 40959-40966) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21069715 J.Teyra, J.Hawkins, H.Zhu, and M.T.Pisabarro (2011).
Studies on the inference of protein binding regions across fold space based on structural similarities.
  Proteins, 79, 499-508.  
21476872 T.Kantyka, K.Plaza, J.Koziel, D.Florczyk, H.R.Stennicke, I.B.Thogersen, J.J.Enghild, G.A.Silverman, S.C.Pak, and J.Potempa (2011).
Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence.
  Biol Chem, 392, 483-489.  
19943908 N.Nickerson, J.Ip, D.T.Passos, and M.J.McGavin (2010).
Comparison of Staphopain A (ScpA) and B (SspB) precursor activation mechanisms reveals unique secretion kinetics of proSspB (Staphopain B), and a different interaction with its cognate Staphostatin, SspC.
  Mol Microbiol, 75, 161-177.  
18026858 B.Władyka, and K.Pustelny (2008).
Regulation of bacterial protease activity.
  Cell Mol Biol Lett, 13, 212-229.  
18294123 G.N.Rudenskaya, and D.V.Pupov (2008).
Cysteine proteinases of microorganisms and viruses.
  Biochemistry (Mosc), 73, 1.  
17391065 B.Vincents, P.Onnerfjord, M.Gruca, J.Potempa, and M.Abrahamson (2007).
Down-regulation of human extracellular cysteine protease inhibitors by the secreted staphylococcal cysteine proteases, staphopain A and B.
  Biol Chem, 388, 437-446.  
17261086 G.Dubin, B.Wladyka, J.Stec-Niemczyk, D.Chmiel, M.Zdzalik, A.Dubin, and J.Potempa (2007).
The staphostatin family of cysteine protease inhibitors in the genus Staphylococcus as an example of parallel evolution of protease and inhibitor specificity.
  Biol Chem, 388, 227-235.  
15716447 L.N.Shaw, E.Golonka, G.Szmyd, S.J.Foster, J.Travis, and J.Potempa (2005).
Cytoplasmic control of premature activation of a secreted protease zymogen: deletion of staphostatin B (SspC) in Staphylococcus aureus 8325-4 yields a profound pleiotropic phenotype.
  J Bacteriol, 187, 1751-1762.  
16333395 M.A.Meehl, J.S.Pinkner, P.J.Anderson, S.J.Hultgren, and M.G.Caparon (2005).
A novel endogenous inhibitor of the secreted streptococcal NAD-glycohydrolase.
  PLoS Pathog, 1, e35.  
16045611 T.F.Kagawa, P.W.O'toole, and J.C.Cooney (2005).
SpeB-Spi: a novel protease-inhibitor pair from Streptococcus pyogenes.
  Mol Microbiol, 57, 650-666.  
15897280 T.Imamura, S.Tanase, G.Szmyd, A.Kozik, J.Travis, and J.Potempa (2005).
Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus.
  J Exp Med, 201, 1669-1676.  
15576326 E.Golonka, R.Filipek, A.Sabat, A.Sinczak, and J.Potempa (2004).
Genetic characterization of staphopain genes in Staphylococcus aureus.
  Biol Chem, 385, 1059-1067.  
15255187 G.Dubin, J.Stec-Niemczyk, T.Dylag, J.Silberring, A.Dubin, and J.Potempa (2004).
Characterisation of a highly specific, endogenous inhibitor of cysteine protease from Staphylococcus epidermidis, a new member of the staphostatin family.
  Biol Chem, 385, 543-546.  
14621990 G.Dubin, M.Krajewski, G.Popowicz, J.Stec-Niemczyk, M.Bochtler, J.Potempa, A.Dubin, and T.A.Holak (2003).
A novel class of cysteine protease inhibitors: solution structure of staphostatin A from Staphylococcus aureus.
  Biochemistry, 42, 13449-13456.
PDB code: 1oh1
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. Where a reference describes a PDB structure, the PDB code is shown on the right.