PDBsum entry 1no0

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Hydrolase PDB id
Protein chain
316 a.a.
_CA ×4
Waters ×185
Superseded by: 1os0 1os0
PDB id:
Name: Hydrolase
Title: Thermolysin with an alpha-amino phosphinic inhibitor
Structure: Thermolysin. Chain: a. Ec:
Source: Bacillus thermoproteolyticus. Bacteria
2.10Å     R-factor:   0.147     R-free:   0.179
Authors: M.Selkti,A.Tomas,T.Prange
Key ref:
M.Selkti et al. (2003). Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition. Acta Crystallogr D Biol Crystallogr, 59, 1200-1205. PubMed id: 12832763 DOI: 10.1107/S0907444903010060
15-Jan-03     Release date:   04-Feb-03    
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+)


DOI no: 10.1107/S0907444903010060 Acta Crystallogr D Biol Crystallogr 59:1200-1205 (2003)
PubMed id: 12832763  
Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.
M.Selkti, A.Tomas, J.F.Gaucher, T.Prangé, M.C.Fournié-Zaluski, H.Chen, B.P.Roques.
A new alpha-aminophosphinic compound able to inhibit both zinc-containing exopeptidases and endopeptidases has been crystallized with TLN as a model in order to investigate the mode of zinc recognition by the phosphinic moiety and to evaluate the potential role of the free alpha-amino group in the formation of enzyme-inhibitor complexes. In addition to the main interactions between the backbone of the inhibitor and the enzyme active site, it is observed that the phosphinic group acts as a distorted bidentate ligand for the zinc ion, while the free alpha-amino function does not directly participate in interactions within the active site. Association of the present data and the K(i) values of various analogues of the inhibitor towards TLN and neprilysin suggests differences in the hydrophobicity of the S(1)-S(2) domains of the enzymes. This could be taken into account in the design of selective inhibitors.
  Selected figure(s)  
Figure 3.
Figure 3 Stereoscopic view of the interactions between the phosphinic inhibitor (1) and TLN in the crystal. Polar bonds are dashed.
Figure 4.
Figure 4 The NEP (Oefner et al., 2000[Oefner, C., D'Arcy, A., Hennig, M., Winkler, F. K. & Dale, G. E. (2000). J. Mol. Biol. 296, 341-349.]) and TLN active sites superimposed using a LSQ fit of their sequences X-H-X[3]-H-X and X-Q-X residues, plus the Zn atom. The two inhibitors (1) for TLN and phosphoramidon for NEP (in plain blue) are shown in their bound states: stereoscopic view, RASMOL program (Merritt & Bacon, 1997[Merritt, E. A. & Bacon, D. J. (1997). Methods Enzymol. 277, 505-524.]).
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2003, 59, 1200-1205) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20640477 S.Kostenko, M.T.Khan, I.Sylte, and U.Moens (2011).
The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor.
  Cell Mol Life Sci, 68, 289-301.  
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