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PDBsum entry 1gec

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Hydrolase/hydrolase inhibitor PDB id
1gec
Jmol
Contents
Protein chain
216 a.a. *
Ligands
PHQ-LEU-VAL-GLY-
0HQ
Waters ×117
* Residue conservation analysis
PDB id:
1gec
Name: Hydrolase/hydrolase inhibitor
Title: Glycyl endopeptidase-complex with benzyloxycarbonyl-leucine- glycine-methylene covalently bound to cysteine 25
Structure: Glycyl endopeptidase. Chain: e. Benzyloxycarbonyl-leucine-valine-glycine-methylen inhibitor. Chain: i. Engineered: yes
Source: Carica papaya. Papaya. Organism_taxid: 3649. Synthetic: yes
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.196     R-free:   0.258
Authors: B.P.Ohara,A.M.Hemmings,D.J.Buttle,L.H.Pearl
Key ref:
B.P.O'Hara et al. (1995). Crystal structure of glycyl endopeptidase from Carica papaya: a cysteine endopeptidase of unusual substrate specificity. Biochemistry, 34, 13190-13195. PubMed id: 7548082 DOI: 10.1021/bi00040a034
Date:
25-May-95     Release date:   07-Dec-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05994  (PAPA4_CARPA) -  Papaya proteinase 4
Seq:
Struc:
348 a.a.
216 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.25  - Glycyl endopeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Gly-|-Xaa, in proteins and in small molecule substrates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     1 term  

 

 
DOI no: 10.1021/bi00040a034 Biochemistry 34:13190-13195 (1995)
PubMed id: 7548082  
 
 
Crystal structure of glycyl endopeptidase from Carica papaya: a cysteine endopeptidase of unusual substrate specificity.
B.P.O'Hara, A.M.Hemmings, D.J.Buttle, L.H.Pearl.
 
  ABSTRACT  
 
Glycyl endopeptidase is a cysteine endopeptidase of the papain family, characterized by specificity for cleavage C-terminal to glycyl residues only and by resistance to inhibition by members of the cystatin family of cysteine proteinase inhibitors. Glycyl endopeptidase has been crystallized from high salt with a substrate-like inhibitor covalently bound to the catalytic Cys 25. The structure has been solved by molecular replacement with the structure of papain and refined at 2.1 A to an R factor of 0.196 (Rfree = 0.258) with good geometry. The structure of the S1 substrate binding site of glycyl endopeptidase differs from that of papain by the substitution of glycines at residues 23 and 65 in papain, with glutamic acid and arginine, respectively, in glycyl endopeptidase. The side chains of these residues form a barrier across the binding pocket, effectively excluding substrate residues with large side chains from the S1 subsite. The constriction of this subsite in glycyl endopeptidase explains the unique specificity of this enzyme for cleavage after glycyl residues and is a major component of its resistance to inhibition by cystatins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
16377622 S.Ishii, T.Yano, and H.Hayashi (2006).
Expression and characterization of the peptidase domain of Streptococcus pneumoniae ComA, a bifunctional ATP-binding cassette transporter involved in quorum sensing pathway.
  J Biol Chem, 281, 4726-4731.  
15502326 M.C.Oliver-Salvador, L.A.González-Ramírez, J.A.Gavira, M.Soriano-García, and J.M.García-Ruiz (2004).
Purification, crystallization and preliminary X-ray analysis of mexicain.
  Acta Crystallogr D Biol Crystallogr, 60, 2058-2060.  
14694194 M.Zhu, F.Shao, R.W.Innes, J.E.Dixon, and Z.Xu (2004).
The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site.
  Proc Natl Acad Sci U S A, 101, 302-307.
PDB code: 1ukf
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
12619677 K.Ito, X.Ma, N.Azmi, H.S.Huang, M.Fujii, and T.Yoshimoto (2003).
Novel aminopeptidase specific for glycine from Actinomucor elegans.
  Biosci Biotechnol Biochem, 67, 83-88.  
10592261 N.D.Rawlings, and A.J.Barrett (2000).
MEROPS: the peptidase database.
  Nucleic Acids Res, 28, 323-325.  
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.  
10329692 J.Herold, S.G.Siddell, and A.E.Gorbalenya (1999).
A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold .
  J Biol Chem, 274, 14918-14925.  
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.  
9233788 S.C.Johnston, C.N.Larsen, W.J.Cook, K.D.Wilkinson, and C.P.Hill (1997).
Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
  EMBO J, 16, 3787-3796.
PDB code: 1uch
  9165062 W.Baumeister, Z.Cejka, M.Kania, and E.Seemüller (1997).
The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
  Biol Chem, 378, 121-130.  
8973203 D.Maes, J.Bouckaert, F.Poortmans, L.Wyns, and Y.Looze (1996).
Structure of chymopapain at 1.7 A resolution.
  Biochemistry, 35, 16292-16298.
PDB code: 1yal
8939744 M.R.Groves, M.A.Taylor, M.Scott, N.J.Cummings, R.W.Pickersgill, and J.A.Jenkins (1996).
The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.
  Structure, 4, 1193-1203.
PDB code: 1pci
8942638 N.A.Katerelos, and P.W.Goodenough (1996).
Rapid kinetic studies and structural determination of a cysteine proteinase mutant imply that residue 158 in caricain has a major effect upon the ability of the active site histidine to protonate a dipyridyl probe.
  Biochemistry, 35, 14763-14772.  
  8896443 R.Coulombe, P.Grochulski, J.Sivaraman, R.Ménard, J.S.Mort, and M.Cygler (1996).
Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
  EMBO J, 15, 5492-5503.
PDB code: 1cjl
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.