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PDBsum entry 1y3g

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protein ligands metals links
Hydrolase PDB id
1y3g
Jmol PyMol
Contents
Protein chain
316 a.a. *
Ligands
DMS ×2
3PL-AMM-LEU
Metals
_CA ×4
_ZN
Waters ×127
* Residue conservation analysis
PDB id:
1y3g
Name: Hydrolase
Title: Crystal structure of a silanediol protease inhibitor bound to thermolysin
Structure: Thermolysin. Chain: e. Ec: 3.4.24.27
Source: Bacillus thermoproteolyticus. Organism_taxid: 1427
Biol. unit: Monomer (from PQS)
Resolution:
2.10Å     R-factor:   0.158     R-free:   0.225
Authors: D.H.Juers,J.Kim,B.W.Matthews,S.M.Sieburth
Key ref:
D.H.Juers et al. (2005). Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin. Biochemistry, 44, 16524-16528. PubMed id: 16342943 DOI: 10.1021/bi051346v
Date:
24-Nov-04     Release date:   17-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00800  (THER_BACTH) -  Thermolysin
Seq:
Struc:
 
Seq:
Struc:
548 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     metalloendopeptidase activity     1 term  

 

 
DOI no: 10.1021/bi051346v Biochemistry 44:16524-16528 (2005)
PubMed id: 16342943  
 
 
Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin.
D.H.Juers, J.Kim, B.W.Matthews, S.M.Sieburth.
 
  ABSTRACT  
 
Dialkylsilanediols have been found to be an effective functional group for the design of active-site-directed protease inhibitors, including aspartic (HIV protease) and metallo (ACE and thermolysin) proteases. The use of silanediols is predicated on its resemblance to the hydrated carbonyl transition-state structure of amide hydrolysis. This concept has been tested by replacing the presumed tetrahedral carbon of a thermolysin substrate with a silanediol group, resulting in an inhibitor with an inhibition constant K(i) = 40 nM. The structure of the silanediol bound to the active site of thermolysin was found to have a conformation very similar to that of a corresponding phosphonamidate inhibitor (K(i) = 10 nM). In both cases, a single oxygen is within bonding distance to the active-site zinc ion, mimicking the presumed tetrahedral transition state. There are binding differences that appear to be related to the presence or absence of protons on the oxygens attached to the silicon or phosphorus. This is the first crystal structure of an organosilane bound to the active site of a protease.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19496083 W.P.Lippert, C.Burschka, K.Götz, M.Kaupp, D.Ivanova, C.Gaudon, Y.Sato, P.Antony, N.Rochel, D.Moras, H.Gronemeyer, and R.Tacke (2009).
Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology.
  ChemMedChem, 4, 1143-1152.
PDB codes: 2zxz 2zy0
18022977 R.Tacke, F.Popp, B.Müller, B.Theis, C.Burschka, A.Hamacher, M.U.Kassack, D.Schepmann, B.Wünsch, U.Jurva, and E.Wellner (2008).
Sila-haloperidol, a silicon analogue of the dopamine (D2) receptor antagonist haloperidol: synthesis, pharmacological properties, and metabolic fate.
  ChemMedChem, 3, 152-164.  
17096442 I.Bertini, V.Calderone, M.Fragai, C.Luchinat, M.Maletta, and K.J.Yeo (2006).
Snapshots of the reaction mechanism of matrix metalloproteinases.
  Angew Chem Int Ed Engl, 45, 7952-7955.
PDB codes: 2oxu 2oxw 2oxz 2oy2 2oy4
16680577 J.F.Fisher, and S.Mobashery (2006).
Recent advances in MMP inhibitor design.
  Cancer Metastasis Rev, 25, 115-136.  
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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