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PDBsum entry 5est
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Hydrolase/hydrolase inhibitor PDB id
5est

 

 

 

 

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Contents
Protein chain
240 a.a. *
Ligands
0P2
SO4
Metals
_CA
Waters ×202
* Residue conservation analysis
PDB id:
5est
Name: Hydrolase/hydrolase inhibitor
Title: Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate
Structure: Elastase. Chain: e. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Tissue: pancreas
Resolution:
2.09Å     R-factor:   0.150    
Authors: L.H.Takahashi,R.Radhakrishnan,R.E.Rosenfieldjunior,E.F.Meyerjunior
Key ref:
L.H.Takahashi et al. (1989). Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate. Biochemistry, 28, 7610-7617. PubMed id: 2611205 DOI: 10.1021/bi00445a016
Date:
15-May-89     Release date:   15-Apr-92    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00772  (CELA1_PIG) -  Chymotrypsin-like elastase family member 1 from Sus scrofa
Seq:
Struc: 		266 a.a.
240 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.3.4.21.36  - pancreatic elastase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.

 

 
DOI no: 10.1021/bi00445a016 Biochemistry 28:7610-7617 (1989)
PubMed id: 2611205  
 
 
Crystallographic analysis of the inhibition of porcine pancreatic elastase by a peptidyl boronic acid: structure of a reaction intermediate.
L.H.Takahashi, R.Radhakrishnan, R.E.Rosenfield, E.F.Meyer.
 
  ABSTRACT  
 
The crystal structure of porcine pancreatic elastase (PPE) complexed to carbobenzoxy-alanylisoleucine-boronic acid (ZAIB) is reported to 2.09-A resolution and refined to an R factor of 0.15. This is the first reported structural analysis of PPE with an isoleucine residu in the primary specificity pocket. The results include (1) marked displacement of the inhibitor out of the active site leading to (2) a close (2.2 A) direct contact between B (boron atom of the inhibitor) and N epsilon of His-57 and also (3) covalent bonding (1.5 A) to O gamma of Ser-195. A scheme for the mechanism of inhibition of PPE by ZAIB is proposed. A comparison with a peptidyl difluoromethyl ketone-PPE complex (Ki = 9.5 microns) is made to explain the strong inhibition of PPE by ZAIB (Ki = 0.3 micron). These results lead us to characterize this structure as a time- and space-averaged reaction intermediate, providing fresh insight into the cramped dimensions available in enzymatic catalyses.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18250198 G.Denecker, P.Ovaere, P.Vandenabeele, and W.Declercq (2008).
Caspase-14 reveals its secrets.
  J Cell Biol, 180, 451-458.  
16754679 B.Liu, C.J.Schofield, and R.C.Wilmouth (2006).
Structural analyses on intermediates in serine protease catalysis.
  J Biol Chem, 281, 24024-24035.
PDB codes: 2bb4 2bd2 2bd3 2bd4 2bd5 2bd7 2bd8 2bd9 2bda 2bdb 2bdc 2h1u
17083959 X.Ding, B.F.Rasmussen, G.A.Petsko, and D.Ringe (2006).
Direct crystallographic observation of an acyl-enzyme intermediate in the elastase-catalyzed hydrolysis of a peptidyl ester substrate: Exploiting the "glass transition" in protein dynamics.
  Bioorg Chem, 34, 410-423.  
12416979 C.C.Tseng, S.D.Bruner, R.M.Kohli, M.A.Marahiel, C.T.Walsh, and S.A.Sieber (2002).
Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase.
  Biochemistry, 41, 13350-13359.  
10738204 I.Nakanishi, T.Kinoshita, A.Sato, and T.Tada (2000).
Structure of porcine pancreatic elastase complexed with FR901277, a novel macrocyclic inhibitor of elastases, at 1.6 A resolution.
  Biopolymers, 53, 434-445.
PDB code: 1qr3
10455164 P.Taylor, V.Anderson, J.Dowden, S.L.Flitsch, N.J.Turner, K.Loughran, and M.D.Walkinshaw (1999).
Novel mechanism of inhibition of elastase by beta-lactams is defined by two inhibitor crystal complexes.
  J Biol Chem, 274, 24901-24905.  
8189835 P.D.Edwards, and P.R.Bernstein (1994).
Synthetic inhibitors of elastase.
  Med Res Rev, 14, 127-194.  
  1304887 E.Meyer (1992).
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.
  Protein Sci, 1, 1543-1562.  
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 codes are shown on the right.

 

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