spacer
spacer

PDBsum entry 1ef7

Go to PDB code: 
protein Protein-protein interface(s) links
Hydrolase PDB id
1ef7
Jmol
Contents
Protein chain
242 a.a. *
Waters ×118
* Residue conservation analysis
PDB id:
1ef7
Name: Hydrolase
Title: Crystal structure of human cathepsin x
Structure: Cathepsin x. Chain: a, b. Ec: 3.4.18.1
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver
Biol. unit: Dimer (from PQS)
Resolution:
2.67Å     R-factor:   0.183     R-free:   0.226
Authors: G.Guncar,I.Klemencic,B.Turk,V.Turk,A.Karaoglanovic-Carmona,L D.Turk
Key ref:
G.Guncar et al. (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. PubMed id: 10745011 DOI: 10.1016/S0969-2126(00)00108-8
Date:
07-Feb-00     Release date:   15-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9UBR2  (CATZ_HUMAN) -  Cathepsin Z
Seq:
Struc:
303 a.a.
242 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.18.1  - Cathepsin X.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Liberation of C-terminal amino acid residue, with broad specificity, but lacks action on C-terminal proline.
 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(00)00108-8 Structure 8:305-313 (2000)
PubMed id: 10745011  
 
 
Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease.
G.Guncar, I.Klemencic, B.Turk, V.Turk, A.Karaoglanovic-Carmona, L.Juliano, D.Turk.
 
  ABSTRACT  
 
BACKGROUND: Cathepsin X is a widespread, abundantly expressed papain-like mammalian lysosomal cysteine protease. It exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity and shares a similar activity profile with cathepsin B. The latter has been implicated in normal physiological events as well as in various pathological states such as rheumatoid arthritis, Alzheimer's disease and cancer progression. Thus the question is raised as to which of the two enzyme activities has actually been monitored. RESULTS: The crystal structure of human cathepsin X has been determined at 2.67 A resolution. The structure shares the common features of a papain-like enzyme fold, but with a unique active site. The most pronounced feature of the cathepsin X structure is the mini-loop that includes a short three-residue insertion protruding into the active site of the protease. The residue Tyr27 on one side of the loop forms the surface of the S1 substrate-binding site, and His23 on the other side modulates both carboxy-monopeptidase as well as carboxy-dipeptidase activity of the enzyme by binding the C-terminal carboxyl group of a substrate in two different sidechain conformations. CONCLUSIONS: The structure of cathepsin X exhibits a binding surface that will assist in the design of specific inhibitors of cathepsin X as well as of cathepsin B and thereby help to clarify the physiological roles of both proteases.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Chemical structures of CA074 and CA030 inhibitors.
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 305-313) copyright 2000.  
  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
20124702 P.D.Adams, P.V.Afonine, G.Bunkóczi, V.B.Chen, I.W.Davis, N.Echols, J.J.Headd, L.W.Hung, G.J.Kapral, R.W.Grosse-Kunstleve, A.J.McCoy, N.W.Moriarty, R.Oeffner, R.J.Read, D.C.Richardson, J.S.Richardson, T.C.Terwilliger, and P.H.Zwart (2010).
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
  Acta Crystallogr D Biol Crystallogr, 66, 213-221.  
  19262176 J.Kos, Z.Jevnikar, and N.Obermajer (2009).
The role of cathepsin X in cell signaling.
  Cell Adh Migr, 3, 164-166.  
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.  
19433310 N.Obermajer, B.Doljak, P.Jamnik, U.P.Fonović, and J.Kos (2009).
Cathepsin X cleaves the C-terminal dipeptide of alpha- and gamma-enolase and impairs survival and neuritogenesis of neuronal cells.
  Int J Biochem Cell Biol, 41, 1685-1696.  
18959767 A.Tsuji, Y.Kikuchi, K.Ogawa, H.Saika, K.Yuasa, and M.Nagahama (2008).
Purification and characterization of cathepsin B-like cysteine protease from cotyledons of daikon radish, Raphanus sativus.
  FEBS J, 275, 5429-5443.  
18453687 T.C.Terwilliger, R.W.Grosse-Kunstleve, P.V.Afonine, N.W.Moriarty, P.D.Adams, R.J.Read, P.H.Zwart, and L.W.Hung (2008).
Iterative-build OMIT maps: map improvement by iterative model building and refinement without model bias.
  Acta Crystallogr D Biol Crystallogr, 64, 515-524.  
16777845 T.Hogg, K.Nagarajan, S.Herzberg, L.Chen, X.Shen, H.Jiang, M.Wecke, C.Blohmke, R.Hilgenfeld, and C.L.Schmidt (2006).
Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum.
  J Biol Chem, 281, 25425-25437.
PDB code: 2ghu
16307485 L.Puzer, S.S.Cotrin, M.H.Cezari, I.Y.Hirata, M.A.Juliano, I.Stefe, D.Turk, B.Turk, L.Juliano, and A.K.Carmona (2005).
Recombinant human cathepsin X is a carboxymonopeptidase only: a comparison with cathepsins B and L.
  Biol Chem, 386, 1191-1195.  
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.  
14630920 S.Hashmi, J.Zhang, Y.Oksov, and S.Lustigman (2004).
The Caenorhabditis elegans cathepsin Z-like cysteine protease, Ce-CPZ-1, has a multifunctional role during the worms' development.
  J Biol Chem, 279, 6035-6045.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12674320 M.Zaidi, H.C.Blair, B.S.Moonga, E.Abe, and C.L.Huang (2003).
Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics.
  J Bone Miner Res, 18, 599-609.  
11517939 R.Ménard, C.Therrien, P.Lachance, T.Sulea, H.Qo, A.D.Alvarez-Hernandez, and W.R.Roush (2001).
Cathepsins X and B display distinct activity profiles that can be exploited for inhibitor design.
  Biol Chem, 382, 839-845.  
10951198 I.Klemencic, A.K.Carmona, M.H.Cezari, M.A.Juliano, L.Juliano, G.Guncar, D.Turk, I.Krizaj, V.Turk, and B.Turk (2000).
Biochemical characterization of human cathepsin X revealed that the enzyme is an exopeptidase, acting as carboxymonopeptidase or carboxydipeptidase.
  Eur J Biochem, 267, 5404-5412.  
11667982 P.J.Wolters, and H.A.Chapman (2000).
Importance of lysosomal cysteine proteases in lung disease.
  Respir Res, 1, 170-177.  
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.