PDBsum entry 3tmn

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Hydrolase/hydrolase inhibitor PDB id
Protein chain
316 a.a. *
_CA ×4
Waters ×173
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: The binding of l-valyl-l-tryptophan to crystalline thermolys illustrates the mode of interaction of a product of peptide hydrolysis
Structure: Thermolysin. Chain: e. Ec:
Source: Bacillus thermoproteolyticus. Organism_taxid: 1427
Biol. unit: Tetramer (from PQS)
1.70Å     R-factor:   0.173    
Authors: H.M.Holden,B.W.Matthews
Key ref: H.M.Holden and B.W.Matthews (1988). The binding of L-valyl-L-tryptophan to crystalline thermolysin illustrates the mode of interaction of a product of peptide hydrolysis. J Biol Chem, 263, 3256-3260. PubMed id: 3343246
29-Jun-87     Release date:   09-Jan-89    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00800  (THER_BACTH) -  Thermolysin
548 a.a.
316 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Thermolysin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe.
      Cofactor: Ca(2+); Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     metalloendopeptidase activity     1 term  


J Biol Chem 263:3256-3260 (1988)
PubMed id: 3343246  
The binding of L-valyl-L-tryptophan to crystalline thermolysin illustrates the mode of interaction of a product of peptide hydrolysis.
H.M.Holden, B.W.Matthews.
Crystallographic analysis of the binding of mercaptoacetyl-L-valyl-L-tryptophan to thermolysin suggests that this inhibitor is hydrolyzed by the crystalline enzyme. The apparent product of hydrolysis, L-valyl-L-tryptophan (Val-Trp), occupies the S1'-S2' subsites of the active site, not the S1-S1' subsites as observed previously for the dipeptide L-alanyl-L-phenylalanine (Ala-Phe). The difference in binding of Val-Trp and Ala-Phe is consistent with the specificity requirements and preferences of thermolysin. The binding of Val-Trp illustrates the mode of interaction of one of the products of peptide hydrolysis. High resolution crystallographic refinement indicates that the valyl amino group makes three hydrogen bonds to the enzyme and to solvent and, in addition, is 2.8 A from the carboxylate of Glu-143. This is the first instance in which a direct interaction has been observed between Glu-143 and the scissile nitrogen. As such, the study directly supports the mechanism of action for thermolysin proposed by Hangauer et al. (Hangauer, D. G., Monzingo, A. F., and Matthews, B. W. (1984) Biochemistry 23, 5730-5741) and, by analogy, indirectly supports the similar mechanism proposed for carboxypeptidase A (Monzingo, A. F., and Matthews, B. W. (1984) Biochemistry 23, 5724-5729).

Literature references that cite this PDB file's key reference

  PubMed id Reference
20161624 R.Wu, P.Hu, S.Wang, Z.Cao, and Y.Zhang (2009).
Flexibility of Catalytic Zinc Coordination in Thermolysin and HDAC8: A Born-Oppenheimer ab initio QM/MM Molecular Dynamics Study.
  J Chem Theory Comput, 6, 337.  
19286830 T.Fober, M.Mernberger, G.Klebe, and E.Hüllermeier (2009).
Evolutionary construction of multiple graph alignments for the structural analysis of biomolecules.
  Bioinformatics, 25, 2110-2117.  
17516427 E.Proschak, M.Rupp, S.Derksen, and G.Schneider (2008).
Shapelets: possibilities and limitations of shape-based virtual screening.
  J Comput Chem, 29, 108-114.  
18074211 G.Lutfullah, F.Amin, Z.Khan, N.Azhar, M.K.Azim, S.Noor, and K.Shoukat (2008).
Homology modeling of hemagglutinin/protease [HA/P (vibriolysin)] from Vibrio cholerae: sequence comparision, residue interactions and molecular mechanism.
  Protein J, 27, 105-114.  
  18959747 L.A.Bruce, J.A.Sigman, D.Randall, S.Rodriguez, M.M.Song, Y.Dai, D.E.Elmore, A.Pabon, M.J.Glucksman, and A.J.Wolfson (2008).
Hydrogen bond residue positioning in the 599-611 loop of thimet oligopeptidase is required for substrate selection.
  FEBS J, 275, 5607-5617.  
17452788 G.Prehna, and C.E.Stebbins (2007).
A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.
  Acta Crystallogr D Biol Crystallogr, 63, 628-635.
PDB code: 2p2l
16216010 B.Bauvois, and D.Dauzonne (2006).
Aminopeptidase-N/CD13 (EC inhibitors: chemistry, biological evaluations, and therapeutic prospects.
  Med Res Rev, 26, 88.  
15526325 M.Kontoyianni, G.S.Sokol, and L.M.McClellan (2005).
Evaluation of library ranking efficacy in virtual screening.
  J Comput Chem, 26, 11-22.  
10651278 A.C.English, S.H.Done, L.S.Caves, C.R.Groom, and R.E.Hubbard (1999).
Locating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol.
  Proteins, 37, 628-640.
PDB codes: 1tli 1tlx 2tli 2tlx 3tli 4tli 5tli 6tli 7tli 8tli
10092869 S.Kunugi, Y.Yanagi, and K.Oda (1999).
Studies on the formation and stability of a complex between Streptomyces proteinaceous metalloprotease inhibitor and thermolysin.
  Eur J Biochem, 259, 815-820.  
9265630 D.G.McCafferty, I.A.Lessard, and C.T.Walsh (1997).
Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX.
  Biochemistry, 36, 10498-10505.  
7738608 G.Klebe, T.Mietzner, and F.Weber (1994).
Different approaches toward an automatic structural alignment of drug molecules: applications to sterol mimics, thrombin and thermolysin inhibitors.
  J Comput Aided Mol Des, 8, 751-778.  
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