PDBsum entry 8pch

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Hydrolase PDB id
Protein chain
220 a.a. *
Waters ×537
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of porcine cathepsin h determined at 2.1 a resolution: location of the mini-chain c-terminal carboxyl defines cathepsin h aminopeptidase function
Structure: Cathepsin h. Chain: a. Cathepsin h. Chain: p. Ec:
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: spleen. Organ: spleen
Biol. unit: Monomer (from PDB file)
2.10Å     R-factor:   not given     R-free:   0.245
Authors: G.Guncar,M.Podobnik,J.Pungercar,B.Strukelj,V.Turk,D.Turk
Key ref:
G.Guncar et al. (1998). Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function. Structure, 6, 51-61. PubMed id: 9493267 DOI: 10.1016/S0969-2126(98)00007-0
07-Nov-97     Release date:   09-Dec-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O46427  (CATH_PIG) -  Pro-cathepsin H
335 a.a.
220 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Cathepsin H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins, acting as an aminopeptidase (notably, cleaving Arg-|-Xaa bonds) as well as an endopeptidase.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     1 term  


DOI no: 10.1016/S0969-2126(98)00007-0 Structure 6:51-61 (1998)
PubMed id: 9493267  
Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function.
G.Guncar, M.Podobnik, J.Pungercar, B.Strukelj, V.Turk, D.Turk.
BACKGROUND: Cathepsin H is a lysosomal cysteine protease, involved in intracellular protein degradation. It is the only known mono-aminopeptidase in the papain-like family and is reported to be involved in tumor metastasis. The cathepsin H structure was determined in order to investigate the structural basis for its aminopeptidase activity and thus to provide the basis for structure-based design of synthetic inhibitors. RESULTS: The crystal structure of native porcine cathepsin H was determined at 2.1 A resolution. The structure has the typical papain-family fold. The so-called mini-chain, the octapeptide EPQNCSAT, is attached via a disulfide bond to the body of the enzyme and bound in a narrowed active-site cleft, in the substrate-binding direction. The mini-chain fills the region that in related enzymes comprises the non-primed substrate-binding sites from S2 backwards. CONCLUSIONS: The crystal structure of cathepsin H reveals that the mini-chain has a definitive role in substrate recognition and that carbohydrate residues attached to the body of the enzyme are involved in positioning the mini-chain in the active-site cleft. Modeling of a substrate into the active-site cleft suggests that the negatively charged carboxyl group of the C terminus of the mini-chain acts as an anchor for the positively charged N-terminal amino group of a substrate. The observed displacements of the residues within the active-site cleft from their equivalent positions in the papain-like endopeptidases suggest that they form the structural basis for the positioning of both the mini-chain and the substrate, resulting in exopeptidase activity.
  Selected figure(s)  
Figure 6.
Figure 6. Schematic representation of the mini-chain binding. The mini-chain (bold lines) is covalently attached by the Cys80P-Cys205 disulfide bridge to the R-domain. Three other residues of the mini-chain form hydrogen bonds (dashed lines) and stabilize the mini-chain position.
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 51-61) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20860624 M.Renko, U.Požgan, D.Majera, and D.Turk (2010).
Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft.
  FEBS J, 277, 4338-4345.
PDB code: 3k9m
19488406 J.Dvorák, S.T.Mashiyama, M.Sajid, S.Braschi, M.Delcroix, E.L.Schneider, W.H.McKerrow, M.Bahgat, E.Hansell, P.C.Babbitt, C.S.Craik, J.H.McKerrow, and C.R.Caffrey (2009).
SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni.
  PLoS Negl Trop Dis, 3, e449.  
19690370 J.Praaenikar, P.V.Afonine, G.Guncar, P.D.Adams, and D.Turk (2009).
Averaged kick maps: less noise, more signal... and probably less bias.
  Acta Crystallogr D Biol Crystallogr, 65, 921-931.  
18469004 G.Droga-Mazovec, L.Bojic, A.Petelin, S.Ivanova, R.Romih, U.Repnik, G.S.Salvesen, V.Stoka, V.Turk, and B.Turk (2008).
Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues.
  J Biol Chem, 283, 19140-19150.  
18256700 G.Hamilton, J.D.Colbert, A.W.Schuettelkopf, and C.Watts (2008).
Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis.
  EMBO J, 27, 499-508.  
18515357 I.Redzynia, A.Ljunggren, M.Abrahamson, J.S.Mort, J.C.Krupa, M.Jaskolski, and G.Bujacz (2008).
Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B.
  J Biol Chem, 283, 22815-22825.
PDB codes: 3cbj 3cbk
17878156 P.Geraghty, C.M.Greene, M.O'Mahony, S.J.O'Neill, C.C.Taggart, and N.G.McElvaney (2007).
Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression.
  J Biol Chem, 282, 33389-33395.  
16201871 M.E.Than, G.P.Bourenkov, S.Henrich, K.Mann, and W.Bode (2005).
The NC1 dimer of human placental basement membrane collagen IV: does a covalent crosslink exist?
  Biol Chem, 386, 759-766.  
16164419 M.Horn, L.Dolecková-Maresová, L.Rulísek, M.Mása, O.Vasiljeva, B.Turk, T.Gan-Erdene, M.Baudys, and M.Mares (2005).
Activation processing of cathepsin H impairs recognition by its propeptide.
  Biol Chem, 386, 941-947.  
15195995 A.Rossi, Q.Deveraux, B.Turk, and A.Sali (2004).
Comprehensive search for cysteine cathepsins in the human genome.
  Biol Chem, 385, 363-372.  
14735489 M.Fabra, and J.Cerdà (2004).
Ovarian cysteine proteinases in the teleost Fundulus heteroclitus: molecular cloning and gene expression during vitellogenesis and oocyte maturation.
  Mol Reprod Dev, 67, 282-294.  
15215586 O.B.De Oliveira Neto, J.A.Batista, D.J.Rigden, O.L.Franco, R.R.Fragoso, A.C.Monteiro, R.G.Monnerat, and M.F.Grossi-De-Sa (2004).
Molecular cloning of a cysteine proteinase cDNA from the cotton boll weevil Anthonomus grandis (Coleoptera: Curculionidae).
  Biosci Biotechnol Biochem, 68, 1235-1242.  
14581476 T.Cirman, K.Oresić, G.D.Mazovec, V.Turk, J.C.Reed, R.M.Myers, G.S.Salvesen, and B.Turk (2004).
Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins.
  J Biol Chem, 279, 3578-3587.  
12534546 C.Mora, I.Flores, F.Montealegre, and A.Díaz (2003).
Cloning and expression of Blo t 1, a novel allergen from the dust mite Blomia tropicalis, homologous to cysteine proteases.
  Clin Exp Allergy, 33, 28-34.  
12887050 D.K.Nägler, and R.Ménard (2003).
Family C1 cysteine proteases: biological diversity or redundancy?
  Biol Chem, 384, 837-843.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
14515996 J.Dodt, and J.Reichwein (2003).
Human cathepsin H: deletion of the mini-chain switches substrate specificity from aminopeptidase to endopeptidase.
  Biol Chem, 384, 1327-1332.  
12565709 M.Matsuishi, G.Saito, A.Okitani, and H.Kato (2003).
Purification and some properties of cathepsin H from rabbit skeletal muscle.
  Int J Biochem Cell Biol, 35, 474-485.  
12833545 M.Sulpizi, A.Laio, J.VandeVondele, A.Cattaneo, U.Rothlisberger, and P.Carloni (2003).
Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations.
  Proteins, 52, 212-224.  
12668429 M.Sulpizi, U.Rothlisberger, and P.Carloni (2003).
Molecular dynamics studies of caspase-3.
  Biophys J, 84, 2207-2215.  
14621998 O.Vasiljeva, M.Dolinar, V.Turk, and B.Turk (2003).
Recombinant human cathepsin H lacking the mini chain is an endopeptidase.
  Biochemistry, 42, 13522-13528.  
11796715 A.Waghray, D.Keppler, B.F.Sloane, L.Schuger, and Y.Q.Chen (2002).
Analysis of a truncated form of cathepsin H in human prostate tumor cells.
  J Biol Chem, 277, 11533-11538.  
11856830 J.P.Turkenburg, M.B.Lamers, A.M.Brzozowski, L.M.Wright, R.E.Hubbard, S.L.Sturt, and D.H.Williams (2002).
Structure of a Cys25-->Ser mutant of human cathepsin S.
  Acta Crystallogr D Biol Crystallogr, 58, 451-455.
PDB code: 1glo
11910036 M.Horn, M.Baudys, Z.Voburka, I.Kluh, J.Vondrásek, and M.Mares (2002).
Free-thiol Cys331 exposed during activation process is critical for native tetramer structure of cathepsin C (dipeptidyl peptidase I).
  Protein Sci, 11, 933-943.  
11726493 D.Turk, V.Janjić, I.Stern, M.Podobnik, D.Lamba, S.W.Dahl, C.Lauritzen, J.Pedersen, V.Turk, and B.Turk (2001).
Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.
  EMBO J, 20, 6570-6582.
PDB code: 1k3b
11514663 E.Pol, and I.Björk (2001).
Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases.
  Protein Sci, 10, 1729-1738.  
11327826 S.W.Dahl, T.Halkier, C.Lauritzen, I.Dolenc, J.Pedersen, V.Turk, and B.Turk (2001).
Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing.
  Biochemistry, 40, 1671-1678.  
11532926 V.Turk, B.Turk, and D.Turk (2001).
Lysosomal cysteine proteases: facts and opportunities.
  EMBO J, 20, 4629-4633.  
10755408 E.C.del Re, S.Shuja, J.Cai, and M.J.Murnane (2000).
Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas.
  Br J Cancer, 82, 1317-1326.  
10745011 G.Guncar, I.Klemencic, B.Turk, V.Turk, A.Karaoglanovic-Carmona, L.Juliano, and D.Turk (2000).
Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease.
  Structure, 8, 305-313.
PDB code: 1ef7
11667982 P.J.Wolters, and H.A.Chapman (2000).
Importance of lysosomal cysteine proteases in lung disease.
  Respir Res, 1, 170-177.  
10679409 R.J.Riese, and H.A.Chapman (2000).
Cathepsins and compartmentalization in antigen presentation.
  Curr Opin Immunol, 12, 107-113.  
10491143 B.Cigic, and R.H.Pain (1999).
Location of the binding site for chloride ion activation of cathepsin C.
  Eur J Biochem, 264, 944-951.  
10350606 C.Czaplewski, Z.Grzonka, M.Jaskólski, F.Kasprzykowski, M.Kozak, E.Politowska, and J.Ciarkowski (1999).
Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity?
  Biochim Biophys Acta, 1431, 290-305.  
10200176 D.K.Nägler, W.Tam, A.C.Storer, J.C.Krupa, J.S.Mort, and R.Ménard (1999).
Interdependency of sequence and positional specificities for cysteine proteases of the papain family.
  Biochemistry, 38, 4868-4874.  
10022822 G.Guncar, G.Pungercic, I.Klemencic, V.Turk, and D.Turk (1999).
Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
  EMBO J, 18, 793-803.
PDB code: 1icf
10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
  9524065 D.Turk, G.Guncar, M.Podobnik, and B.Turk (1998).
Revised definition of substrate binding sites of papain-like cysteine proteases.
  Biol Chem, 379, 137-147.  
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.