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PDBsum entry 1btu

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protein ligands metals links
Serine protease PDB id
1btu
Jmol
Contents
Protein chain
240 a.a. *
Ligands
SO4
2BL
Metals
_CA
Waters ×206
* Residue conservation analysis
PDB id:
1btu
Name: Serine protease
Title: Porcine pancreatic elastase complexed with (3s, 4r)-1- toluenesulphonyl-3-ethyl-azetidin-2-one-4-carboxylic acid
Structure: Elastase. Chain: a. Synonym: ppe. Other_details: porcine pancreatic elastase
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas
Resolution:
1.60Å     R-factor:   0.192     R-free:   0.220
Authors: R.C.Wilmouth,I.J.Clifton,C.J.Schofield
Key ref:
R.C.Wilmouth et al. (1998). Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex. Biochemistry, 37, 17506-17513. PubMed id: 9860865 DOI: 10.1021/bi9816249
Date:
01-Sep-98     Release date:   16-Feb-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00772  (CELA1_PIG) -  Chymotrypsin-like elastase family member 1
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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     pancreas morphogenesis   12 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
DOI no: 10.1021/bi9816249 Biochemistry 37:17506-17513 (1998)
PubMed id: 9860865  
 
 
Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex.
R.C.Wilmouth, N.J.Westwood, K.Anderson, W.Brownlee, T.D.Claridge, I.J.Clifton, G.J.Pritchard, R.T.Aplin, C.J.Schofield.
 
  ABSTRACT  
 
beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall biosynthesis remain among the most important therapeutic agents in clinical use. beta-Lactams have more recently been developed as inhibitors of serine proteases including elastase. All therapeutically useful beta-lactam inhibitors operate via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme complexes. Presently, it is difficult to predict which beta-lactams will form stable acyl-enzyme complexes with serine enzymes. Further, the factors that result in the seemingly special nature of beta-lactams versus other acylating agents are unclear-if indeed they exist. Here we present the 1.6 A resolution crystal structure of a stable acyl-enzyme complex formed between porcine pancreatic elastase and a representative monocyclic beta-lactam, which forms a simple acyl-enzyme. The structure shows that the ester carbonyl is not located within the oxyanion hole and the "hydrolytic" water is displaced. Combined with additional kinetic and mass spectrometric data, the structure allows the rationalization of the low degree of hydrolytic lability observed for the beta-lactam-derived acyl-enzyme complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18808119 P.A.Sigala, D.A.Kraut, J.M.Caaveiro, B.Pybus, E.A.Ruben, D.Ringe, G.A.Petsko, and D.Herschlag (2008).
Testing geometrical discrimination within an enzyme active site: constrained hydrogen bonding in the ketosteroid isomerase oxyanion hole.
  J Am Chem Soc, 130, 13696-13708.
PDB codes: 2inx 3cpo
17894328 P.Singh, S.A.Williams, M.H.Shah, T.Lectka, G.J.Pritchard, J.T.Isaacs, and S.R.Denmeade (2008).
Mechanistic insights into the inhibition of prostate specific antigen by beta-lactam class compounds.
  Proteins, 70, 1416-1428.  
17553791 J.Lee, A.R.Feldman, B.Delmas, and M.Paetzel (2007).
Crystal structure of the VP4 protease from infectious pancreatic necrosis virus reveals the acyl-enzyme complex for an intermolecular self-cleavage reaction.
  J Biol Chem, 282, 24928-24937.
PDB codes: 2pnl 2pnm
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
16602823 D.A.Kraut, P.A.Sigala, B.Pybus, C.W.Liu, D.Ringe, G.A.Petsko, and D.Herschlag (2006).
Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole.
  PLoS Biol, 4, e99.
PDB codes: 2b32 2pzv
12554935 J.Aÿ, K.Hilpert, N.Krauss, J.Schneider-Mergener, and W.Höhne (2003).
Structure of a hybrid squash inhibitor in complex with porcine pancreatic elastase at 1.8 A resolution.
  Acta Crystallogr D Biol Crystallogr, 59, 247-254.
PDB code: 1mcv
11741964 M.Paetzel, R.E.Dalbey, and N.C.Strynadka (2002).
Crystal structure of a bacterial signal peptidase apoenzyme: implications for signal peptide binding and the Ser-Lys dyad mechanism.
  J Biol Chem, 277, 9512-9519.
PDB code: 1kn9
10739939 M.Würtele, M.Hahn, K.Hilpert, and W.Höhne (2000).
Atomic resolution structure of native porcine pancreatic elastase at 1.1 A.
  Acta Crystallogr D Biol Crystallogr, 56, 520-523.
PDB code: 1qnj
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.  
10387042 R.C.Wilmouth, S.Kassamally, N.J.Westwood, R.J.Sheppard, T.D.Claridge, R.T.Aplin, P.A.Wright, G.J.Pritchard, and C.J.Schofield (1999).
Mechanistic insights into the inhibition of serine proteases by monocyclic lactams.
  Biochemistry, 38, 7989-7998.
PDB code: 1qgf
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.