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PDBsum entry 1elb
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Hydrolase/hydrolase inhibitor PDB id
1elb

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
240 a.a. *
Ligands
0Z4
SO4
Metals
_CA
Waters ×126
* Residue conservation analysis
PDB id:
1elb
Name: Hydrolase/hydrolase inhibitor
Title: Analogous inhibitors of elastase do not always bind analogously
Structure: Elastase. Chain: a. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas
Resolution:
2.10Å     R-factor:   0.150    
Authors: C.Mattos,B.Rasmussen,X.Ding,G.A.Petsko,D.Ringe
Key ref: C.Mattos et al. (1994). Analogous inhibitors of elastase do not always bind analogously. Nat Struct Biol, 1, 55-58. PubMed id: 7656008
Date:
07-Dec-93     Release date:   22-Jun-94    
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 1:55-58 (1994)
PubMed id: 7656008  
 
 
Analogous inhibitors of elastase do not always bind analogously.
C.Mattos, B.Rasmussen, X.Ding, G.A.Petsko, D.Ringe.
 
  ABSTRACT  
 
It has been assumed that the structure of a single inhibitor complex is sufficient to define the available subsites of an enzyme that has a unique binding site and a uniquely defined mode for ligand binding--the specificity for these subsites can thus be probed by kinetic experiments. Elastase is an enzyme for which these traditional assumptions, which underlie such structural and kinetic studies, do not hold. Three new crystal structures of elastase complexed to chemically similar inhibitors with similar binding affinities reveal a diversity of binding modes as well as two new subsites on elastase. The existence of multiple binding sites and different binding modes for such similar inhibitors indicates that researchers must proceed with caution when using kinetics to map out protein subsites.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21543845 A.Sukhwal, M.Bhattacharyya, and S.Vishveshwara (2011).
Network approach for capturing ligand-induced subtle global changes in protein structures.
  Acta Crystallogr D Biol Crystallogr, 67, 429-439.  
20886466 A.Vulpetti, N.Schiering, and C.Dalvit (2010).
Combined use of computational chemistry, NMR screening, and X-ray crystallography for identification and characterization of fluorophilic protein environments.
  Proteins, 78, 3281-3291.
PDB codes: 3nk8 3nkk
20113043 D.G.Kuroda, D.Y.Vorobyev, and R.M.Hochstrasser (2010).
Ultrafast relaxation and 2D IR of the aqueous trifluorocarboxylate ion.
  J Chem Phys, 132, 044501.  
19085027 J.P.Priestle (2009).
3-D clustering: a tool for high throughput docking.
  J Mol Model, 15, 551-560.  
19176554 R.Brenke, D.Kozakov, G.Y.Chuang, D.Beglov, D.Hall, M.R.Landon, C.Mattos, and S.Vajda (2009).
Fragment-based identification of druggable 'hot spots' of proteins using Fourier domain correlation techniques.
  Bioinformatics, 25, 621-627.  
19016856 G.Meriläinen, W.Schmitz, R.K.Wierenga, and P.Kursula (2008).
The sulfur atoms of the substrate CoA and the catalytic cysteine are required for a productive mode of substrate binding in bacterial biosynthetic thiolase, a thioester-dependent enzyme.
  FEBS J, 275, 6136-6148.
PDB codes: 2vtz 2vu0 2vu1 2vu2
16287115 S.Bhat, and E.O.Purisima (2006).
Molecular surface generation using a variable-radius solvent probe.
  Proteins, 62, 244-261.  
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
11151003 M.L.Lamb, K.W.Burdick, S.Toba, M.M.Young, A.G.Skillman, X.Zou, J.R.Arnold, and I.D.Kuntz (2001).
Design, docking, and evaluation of multiple libraries against multiple targets.
  Proteins, 42, 296-318.  
10679381 G.A.Petsko, and D.Ringe (2000).
Observation of unstable species in enzyme-catalyzed transformations using protein crystallography.
  Curr Opin Chem Biol, 4, 89-94.  
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
10665832 G.K.Farber (1999).
New approaches to rational drug design.
  Pharmacol Ther, 84, 327-332.  
10611647 G.M.Verkhivker, P.A.Rejto, D.Bouzida, S.Arthurs, A.B.Colson, S.T.Freer, D.K.Gehlhaar, V.Larson, B.A.Luty, T.Marrone, and P.W.Rose (1999).
Towards understanding the mechanisms of molecular recognition by computer simulations of ligand-protein interactions.
  J Mol Recognit, 12, 371-389.  
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.  
  10338024 R.Brem, and K.A.Dill (1999).
The effect of multiple binding modes on empirical modeling of ligand docking to proteins.
  Protein Sci, 8, 1134-1143.  
  9761470 J.Liang, H.Edelsbrunner, and C.Woodward (1998).
Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design.
  Protein Sci, 7, 1884-1897.  
9188738 R.T.Koehler, H.O.Villar, K.E.Bauer, and D.L.Higgins (1997).
Ligand-based protein alignment and isozyme specificity of glutathione S-transferase inhibitors.
  Proteins, 28, 202-216.  
8807840 B.K.Shoichet, and I.D.Kuntz (1996).
Predicting the structure of protein complexes: a step in the right direction.
  Chem Biol, 3, 151-156.  
8728658 P.Bamborough, and F.E.Cohen (1996).
Modeling protein-ligand complexes.
  Curr Opin Struct Biol, 6, 236-241.  
8749372 D.Ringe (1995).
What makes a binding site a binding site?
  Curr Opin Struct Biol, 5, 825-829.  
7582978 W.F.Lau, L.Tabernero, J.S.Sack, and E.J.Iwanowicz (1995).
Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.
  Bioorg Med Chem, 3, 1039-1048.  
7922037 C.L.Verlinde, and W.G.Hol (1994).
Structure-based drug design: progress, results and challenges.
  Structure, 2, 577-587.  
7712290 P.M.Colman (1994).
Structure-based drug design.
  Curr Opin Struct Biol, 4, 868-874.  
7784540 W.F.van Gunsteren, P.M.King, and A.E.Mark (1994).
Fundamentals of drug design from a biophysical viewpoint.
  Q Rev Biophys, 27, 435-481.  
9383368 Z.Li, X.Chen, E.Davidson, O.Zwang, C.Mendis, C.S.Ring, W.R.Roush, G.Fegley, R.Li, and P.J.Rosenthal (1994).
Anti-malarial drug development using models of enzyme structure.
  Chem Biol, 1, 31-37.  
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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