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PDBsum entry 1cgh
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Hydrolase/hydrolase inhibitor PDB id
1cgh

 

 

 

 

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Contents
Protein chain
224 a.a. *
Ligands
1ZG
Waters ×435
* Residue conservation analysis
PDB id:
1cgh
Name: Hydrolase/hydrolase inhibitor
Title: Human cathepsin g
Structure: Cathepsin g. Chain: a. Ec: 3.4.21.20
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.80Å     R-factor:   0.190     R-free:   0.240
Authors: P.Hof,W.Bode
Key ref: P.Hof et al. (1996). The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities. Embo J, 15, 5481-5491. PubMed id: 8896442
Date:
26-Jun-96     Release date:   07-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08311  (CATG_HUMAN) -  Cathepsin G from Homo sapiens
Seq:
Struc: 		255 a.a.
224 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.20  - cathepsin G.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Specificity similar to chymotrypsin C.

 

 
Embo J 15:5481-5491 (1996)
PubMed id: 8896442  
 
 
The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.
P.Hof, I.Mayr, R.Huber, E.Korzus, J.Potempa, J.Travis, J.C.Powers, W.Bode.
 
  ABSTRACT  
 
The crystal structure of human neutrophil cathepsin G, complexed with the peptidyl phosphonate inhibitor Suc-Val-Pro-PheP-(OPh)2, has been determined to a resolution of 1.8 A using Patterson search techniques. The cathepsin G structure shows the polypeptide fold characteristic of trypsin-like serine proteinases and is especially similar to rat mast cell proteinase II. Unique to cathepsin G, however, is the presence of Glu226 (chymotrypsinogen numbering), which is situated at the bottom of the S1 specificity pocket, dividing it into two compartments. For this reason, the benzyl side chain of the inhibitor PheP residue does not fully occupy the pocket but is, instead, located at its entrance. Its positively charged equatorial edge is involved in a favourable electrostatic interaction with the negatively charged carboxylate group of Glu226. Arrangement of this Glu226 carboxylate would also allow accommodation of a Lys side chain in this S1 pocket, in agreement with the recently observed cathepsin G preference for Lys and Phe at P1. The cathepsin G complex with the covalently bound phosphonate inhibitor mimics a tetrahedral substrate intermediate. A comparison of the Arg surface distributions of cathepsin G, leukocyte elastase and rat mast cell protease II shows no simple common recognition pattern for a mannose-6-phosphate receptor-independent targeting mechanism for sorting of these granular proteinases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20338912 M.Gallwitz, M.Enoksson, M.Thorpe, X.Ge, and L.Hellman (2010).
The extended substrate recognition profile of the dog mast cell chymase reveals similarities and differences to the human chymase.
  Int Immunol, 22, 421-431.  
  19933375 N.N.Trivedi, and G.H.Caughey (2010).
Mast cell peptidases: chameleons of innate immunity and host defense.
  Am J Respir Cell Mol Biol, 42, 257-267.  
19833730 T.Kalupov, M.Brillard-Bourdet, S.Dadé, H.Serrano, J.Wartelle, N.Guyot, L.Juliano, T.Moreau, A.Belaaouaj, and F.Gauthier (2009).
Structural characterization of mouse neutrophil serine proteases and identification of their substrate specificities: relevance to mouse models of human inflammatory diseases.
  J Biol Chem, 284, 34084-34091.  
19325843 B.Gatto, E.Vianini, L.Lucatello, C.Sissi, D.Moltrasio, R.Pescador, R.Porta, and M.Palumbo (2008).
Effective DNA inhibitors of cathepsin g by in vitro selection.
  Int J Mol Sci, 9, 1008-1023.  
17981788 J.Kervinen, M.Abad, C.Crysler, M.Kolpak, A.D.Mahan, J.A.Masucci, S.Bayoumy, M.D.Cummings, X.Yao, M.Olson, L.de Garavilla, L.Kuo, I.Deckman, and J.Spurlino (2008).
Structural basis for elastolytic substrate specificity in rodent alpha-chymases.
  J Biol Chem, 283, 427-436.
PDB code: 2rdl
18627314 M.Olczak, K.Indyk, and T.Olczak (2008).
Reconstitution of human azurocidin catalytic triad and proteolytic activity by site-directed mutagenesis.
  Biol Chem, 389, 955-962.  
17976994 Y.Li, Q.Yang, D.Dou, K.R.Alliston, and W.C.Groutas (2008).
Inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamides.
  Bioorg Med Chem, 16, 692-698.  
17653609 M.Wysocka, A.Legowska, E.Bulak, A.Jaśkiewicz, H.Miecznikowska, A.Lesner, and K.Rolka (2007).
New chromogenic substrates of human neutrophil cathepsin G containing non-natural aromatic amino acid residues in position P(1) selected by combinatorial chemistry methods.
  Mol Divers, 11, 93-99.  
18037126 Y.Tsuchiya, Y.Okuno, K.Hishinuma, A.Ezaki, G.Okada, M.Yamaguchi, T.Chikuma, and H.Hojo (2007).
4-Hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G.
  Free Radic Biol Med, 43, 1604-1615.  
16708409 C.M.Salisbury, and J.A.Ellman (2006).
Rapid identification of potent nonpeptidic serine protease inhibitors.
  Chembiochem, 7, 1034-1037.  
18516248 G.H.Caughey (2006).
A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense.
  Curr Respir Med Rev, 2, 263-277.  
16807745 M.Gallwitz, J.M.Reimer, and L.Hellman (2006).
Expansion of the mast cell chymase locus over the past 200 million years of mammalian evolution.
  Immunogenetics, 58, 655-669.  
15967795 B.Shao, A.Belaaouaj, C.L.Verlinde, X.Fu, and J.W.Heinecke (2005).
Methionine sulfoxide and proteolytic cleavage contribute to the inactivation of cathepsin G by hypochlorous acid: an oxidative mechanism for regulation of serine proteinases by myeloperoxidase.
  J Biol Chem, 280, 29311-29321.  
15741158 L.de Garavilla, M.N.Greco, N.Sukumar, Z.W.Chen, A.O.Pineda, F.S.Mathews, E.Di Cera, E.C.Giardino, G.I.Wells, B.J.Haertlein, J.A.Kauffman, T.W.Corcoran, C.K.Derian, A.J.Eckardt, B.P.Damiano, P.Andrade-Gordon, and B.E.Maryanoff (2005).
A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo.
  J Biol Chem, 280, 18001-18007.
PDB codes: 1t31 1t32
16038610 T.S.Zamolodchikova, E.V.Smirnova, A.N.Andrianov, I.V.Kashparov, O.D.Kotsareva, E.A.Sokolova, K.B.Ignatov, and A.D.Pemberton (2005).
Cloning and molecular modeling of duodenase with respect to evolution of substrate specificity within mammalian serine proteases that have lost a conserved active-site disulfide bond.
  Biochemistry (Mosc), 70, 672-684.  
15106791 S.C.Whitman (2004).
All of the components required for angiotensin II formation are expressed locally in human atherosclerotic lesions, including a long suspected player cathepsin G.
  J Hypertens, 22, 39-42.  
15123647 S.W.Ruggles, R.J.Fletterick, and C.S.Craik (2004).
Characterization of structural determinants of granzyme B reveals potent mediators of extended substrate specificity.
  J Biol Chem, 279, 30751-30759.  
14536074 M.A.Wouters, K.Liu, P.Riek, and A.Husain (2003).
A despecialization step underlying evolution of a family of serine proteases.
  Mol Cell, 12, 343-354.  
12874306 S.Katzif, D.Danavall, S.Bowers, J.T.Balthazar, and W.M.Shafer (2003).
The major cold shock gene, cspA, is involved in the susceptibility of Staphylococcus aureus to an antimicrobial peptide of human cathepsin G.
  Infect Immun, 71, 4304-4312.  
12900423 U.Karlson, G.Pejler, B.Tomasini-Johansson, and L.Hellman (2003).
Extended substrate specificity of rat mast cell protease 5, a rodent alpha-chymase with elastase-like primary specificity.
  J Biol Chem, 278, 39625-39631.  
12437096 A.Gudmundsdóttir (2002).
Cold-adapted and mesophilic brachyurins.
  Biol Chem, 383, 1125-1131.  
12384499 C.Hink-Schauer, E.Estébanez-Perpiñá, E.Wilharm, P.Fuentes-Prior, W.Klinkert, W.Bode, and D.E.Jenne (2002).
The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features.
  J Biol Chem, 277, 50923-50933.
PDB codes: 1mza 1mzd
11985658 H.R.Miller, and A.D.Pemberton (2002).
Tissue-specific expression of mast cell granule serine proteinases and their role in inflammation in the lung and gut.
  Immunology, 105, 375-390.  
12055188 M.I.Plotnick, H.Rubin, and N.M.Schechter (2002).
The effects of reactive site location on the inhibitory properties of the serpin alpha(1)-antichymotrypsin.
  J Biol Chem, 277, 29927-29935.  
11375259 E.Glusa, and C.Adam (2001).
Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries.
  Br J Pharmacol, 133, 422-428.  
11325591 J.Rotonda, M.Garcia-Calvo, H.G.Bull, W.M.Geissler, B.M.McKeever, C.A.Willoughby, N.A.Thornberry, and J.W.Becker (2001).
The three-dimensional structure of human granzyme B compared to caspase-3, key mediators of cell death with cleavage specificity for aspartic acid in P1.
  Chem Biol, 8, 357-368.
PDB code: 1iau
11209755 E.Estébanez-Perpiña, P.Fuentes-Prior, D.Belorgey, M.Braun, R.Kiefersauer, K.Maskos, R.Huber, H.Rubin, and W.Bode (2000).
Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
  Biol Chem, 381, 1203-1214.
PDB code: 1fq3
10660528 J.Duranton, C.Boudier, D.Belorgey, P.Mellet, and J.G.Bieth (2000).
DNA strongly impairs the inhibition of cathepsin G by alpha(1)-antichymotrypsin and alpha(1)-proteinase inhibitor.
  J Biol Chem, 275, 3787-3792.  
10944388 V.Z.Pletnev, T.S.Zamolodchikova, W.A.Pangborn, and W.L.Duax (2000).
Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.
  Proteins, 41, 8.
PDB code: 1euf
10617628 Y.Xu, A.Circolo, H.Jing, Y.Wang, S.V.Narayana, and J.E.Volanakis (2000).
Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding.
  J Biol Chem, 275, 378-385.  
10382669 A.Caputo, J.C.Parrish, M.N.James, J.C.Powers, and R.C.Bleackley (1999).
Electrostatic reversal of serine proteinase substrate specificity.
  Proteins, 35, 415-424.  
10387091 C.Boudier, M.Cadène, and J.G.Bieth (1999).
Inhibition of neutrophil cathepsin G by oxidized mucus proteinase inhibitor. Effect of heparin.
  Biochemistry, 38, 8451-8457.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
10318785 S.Réhault, M.Brillard-Bourdet, M.A.Juliano, L.Juliano, F.Gauthier, and T.Moreau (1999).
New, sensitive fluorogenic substrates for human cathepsin G based on the sequence of serpin-reactive site loops.
  J Biol Chem, 274, 13810-13817.  
10465545 W.C.Groutas, N.M.Schechter, S.He, H.Yu, P.Huang, and J.Tu (1999).
Human chymase inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
  Bioorg Med Chem Lett, 9, 2199-2204.  
9698370 J.Duranton, C.Adam, and J.G.Bieth (1998).
Kinetic mechanism of the inhibition of cathepsin G by alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor.
  Biochemistry, 37, 11239-11245.  
9675278 J.Polanowska, I.Krokoszynska, H.Czapinska, W.Watorek, M.Dadlez, and J.Otlewski (1998).
Specificity of human cathepsin G.
  Biochim Biophys Acta, 1386, 189-198.  
9753698 M.A.Parry, U.Jacob, R.Huber, A.Wisner, C.Bon, and W.Bode (1998).
The crystal structure of the novel snake venom plasminogen activator TSV-PA: a prototype structure for snake venom serine proteinases.
  Structure, 6, 1195-1206.
PDB code: 1bqy
9871614 R.Kuang, R.Venkataraman, S.Ruan, and W.C.Groutas (1998).
Use of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds in the design of potent inhibitors of serine proteinases.
  Bioorg Med Chem Lett, 8, 539-544.  
9271589 O.Chertov, H.Ueda, L.L.Xu, K.Tani, W.J.Murphy, J.M.Wang, O.M.Howard, T.J.Sayers, and J.J.Oppenheim (1997).
Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as chemoattractants for mononuclear cells and neutrophils.
  J Exp Med, 186, 739-747.  
  9260273 S.A.Gillmor, C.S.Craik, and R.J.Fletterick (1997).
Structural determinants of specificity in the cysteine protease cruzain.
  Protein Sci, 6, 1603-1611.
PDB codes: 1aim 2aim
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.

 

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