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PDBsum entry 1qix
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Serine proteinase PDB id
1qix

 

 

 

 

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Contents
Protein chain
240 a.a. *
Ligands
VAL-GLU-PRO-ILE
SO4
Metals
_CA
Waters ×116
* Residue conservation analysis
PDB id:
1qix
Name: Serine proteinase
Title: Porcine pancreatic elastase complexed with human beta-casomorphin-7
Structure: Beta-casomorphin-7. Chain: a. Engineered: yes. Elastase. Chain: b. Synonym: ppe. Other_details: porcine pancreatic elastase
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas
Resolution:
1.90Å     R-factor:   0.172     R-free:   0.219
Authors: R.C.Wilmouth,I.J.Clifton,J.Hajdu,C.J.Schofield
Key ref: R.C.Wilmouth et al. (1997). Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase. Nat Struct Biol, 4, 456-462. PubMed id: 9187653
Date:
18-Jun-99     Release date:   14-Dec-99    
PROCHECK
Go to PROCHECK summary
 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.

 

 
Nat Struct Biol 4:456-462 (1997)
PubMed id: 9187653  
 
 
Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase.
R.C.Wilmouth, I.J.Clifton, C.V.Robinson, P.L.Roach, R.T.Aplin, N.J.Westwood, J.Hajdu, C.J.Schofield.
 
  ABSTRACT  
 
Mass spectrometric screening reveals that an unmodified natural heptapeptide--human beta-casomorphin-7, an internal sequence of human beta-casein that possesses opioid-like activity--reacts with porcine pancreatic elastase to form an unusually stable acyl-enzyme complex at low pH. X-ray crystallographic analysis (to 1.9 A resolution) at pH 5 shows continuous electron density linking the C-terminal isoleucine of beta-casomorphin-7 to Ser 195 through an ester bond. The structure reveals a well defined water molecule (Wat 317), equidistant between the carbon of the ester carbonyl and N epsilon 2 of His 57. Deprotonation of Wat 317 will produce a hydroxide ion positioned to attack the ester carbonyl through the favoured Bürgi-Dunitz trajectory.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21213248 D.V.Palanivelu, A.Goepfert, M.Meury, P.Guye, C.Dehio, and T.Schirmer (2011).
Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA.
  Protein Sci, 20, 492-499.
PDB codes: 2jk8 2vy3 2vza
21351219 Y.Jiang, K.L.Morley, J.D.Schrag, and R.J.Kazlauskas (2011).
Different active-site loop orientation in serine hydrolases versus acyltransferases.
  Chembiochem, 12, 768-776.
PDB code: 3ia2
20112920 d.e. .L.T.Yin, P.Bernhardt, K.L.Morley, Y.Jiang, J.D.Cheeseman, V.Purpero, J.D.Schrag, and R.J.Kazlauskas (2010).
Switching catalysis from hydrolysis to perhydrolysis in Pseudomonas fluorescens esterase.
  Biochemistry, 49, 1931-1942.
PDB codes: 3hea 3hi4
19549826 E.Zakharova, M.P.Horvath, and D.P.Goldenberg (2009).
Structure of a serine protease poised to resynthesize a peptide bond.
  Proc Natl Acad Sci U S A, 106, 11034-11039.
PDB codes: 3fp6 3fp7 3fp8
18820257 K.W.Sanggaard, C.S.Sonne-Schmidt, T.P.Krogager, T.Kristensen, H.G.Wisniewski, I.B.Thøgersen, and J.J.Enghild (2008).
TSG-6 Transfers Proteins between Glycosaminoglycans via a Ser28-mediated Covalent Catalytic Mechanism.
  J Biol Chem, 283, 33919-33926.  
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
16636277 E.S.Radisky, J.M.Lee, C.J.Lu, and D.E.Koshland (2006).
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
  Proc Natl Acad Sci U S A, 103, 6835-6840.
PDB codes: 2age 2agg 2agi 2ah4
16339904 D.Vivares, P.Arnoux, and D.Pignol (2005).
A papain-like enzyme at work: native and acyl-enzyme intermediate structures in phytochelatin synthesis.
  Proc Natl Acad Sci U S A, 102, 18848-18853.
PDB codes: 2btw 2bu3
14675549 A.Vrielink, and N.Sampson (2003).
Sub-Angstrom resolution enzyme X-ray structures: is seeing believing?
  Curr Opin Struct Biol, 13, 709-715.  
14583255 M.A.McDonough, and C.J.Schofield (2003).
New structural insights into the inhibition of serine proteases by cyclic peptides from bacteria.
  Chem Biol, 10, 898-900.  
14583266 U.Matern, C.Schleberger, S.Jelakovic, J.Weckesser, and G.E.Schulz (2003).
Binding structure of elastase inhibitor scyptolin A.
  Chem Biol, 10, 997.
PDB code: 1okx
11896054 G.Katona, R.C.Wilmouth, P.A.Wright, G.I.Berglund, J.Hajdu, R.Neutze, and C.J.Schofield (2002).
X-ray structure of a serine protease acyl-enzyme complex at 0.95-A resolution.
  J Biol Chem, 277, 21962-21970.
PDB code: 1gvk
12210153 J.Antony, N.Gresh, L.Olsen, L.Hemmingsen, C.J.Schofield, and R.Bauer (2002).
Binding of D- and L-captopril inhibitors to metallo-beta-lactamase studied by polarizable molecular mechanics and quantum mechanics.
  J Comput Chem, 23, 1281-1296.  
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
11948789 M.Topf, P.Várnai, C.J.Schofield, and W.G.Richards (2002).
Molecular dynamics simulations of the acyl-enzyme and the tetrahedral intermediate in the deacylation step of serine proteases.
  Proteins, 47, 357-369.  
11514565 N.C.Rockwell, and R.S.Fuller (2001).
Differential utilization of enzyme-substrate interactions for acylation but not deacylation during the catalytic cycle of Kex2 protease.
  J Biol Chem, 276, 38394-38399.  
11297433 N.C.Rockwell, and R.S.Fuller (2001).
Direct measurement of acylenzyme hydrolysis demonstrates rate-limiting deacylation in cleavage of physiological sequences by the processing protease Kex2.
  Biochemistry, 40, 3657-3665.  
11358514 P.A.Wright, R.C.Wilmouth, I.J.Clifton, and C.J.Schofield (2001).
Kinetic and crystallographic analysis of complexes formed between elastase and peptides from beta-casein.
  Eur J Biochem, 268, 2969-2974.
PDB code: 1h9l
9873058 C.Wu, D.H.Robertson, S.J.Hubbard, S.J.Gaskell, and R.J.Beynon (1999).
Proteolysis of native proteins. Trapping of a reaction intermediate.
  J Biol Chem, 274, 1108-1115.  
10387040 H.Jhoti, A.Cleasby, S.Reid, P.J.Thomas, M.Weir, and A.Wonacott (1999).
Crystal structures of thrombin complexed to a novel series of synthetic inhibitors containing a 5,5-trans-lactone template.
  Biochemistry, 38, 7969-7977.
PDB codes: 1qhr 1qj1 1qj6 1qj7
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
9578548 M.P.Weir, S.S.Bethell, A.Cleasby, C.J.Campbell, R.J.Dennis, C.J.Dix, H.Finch, H.Jhoti, C.J.Mooney, S.Patel, C.M.Tang, M.Ward, A.J.Wonacott, and C.W.Wharton (1998).
Novel natural product 5,5-trans-lactone inhibitors of human alpha-thrombin: mechanism of action and structural studies.
  Biochemistry, 37, 6645-6657.
PDB codes: 1awf 1awh
9860865 R.C.Wilmouth, N.J.Westwood, K.Anderson, W.Brownlee, T.D.Claridge, I.J.Clifton, G.J.Pritchard, R.T.Aplin, and C.J.Schofield (1998).
Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex.
  Biochemistry, 37, 17506-17513.
PDB code: 1btu
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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