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PDBsum entry 3qh5

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
3qh5
Jmol
Contents
Protein chain
316 a.a.
Ligands
0A9 ×2
NX6
PG4
PEG ×3
Metals
_CA ×4
_ZN
Waters ×277
PDB id:
3qh5
Name: Hydrolase/hydrolase inhibitor
Title: Structure of thermolysin in complex with n-carbobenzyloxy-l- acid and l-phenylalanine methyl ester
Structure: Thermolysin. Chain: a. Synonym: thermostable neutral proteinase. Ec: 3.4.24.27
Source: Bacillus thermoproteolyticus. Organism_taxid: 1427
Resolution:
1.50Å     R-factor:   0.146     R-free:   0.187
Authors: G.Birrane,B.Bhyravbhatla,M.Navia
Key ref: G.Birrane et al. (2014). Synthesis of Aspartame by Thermolysin: An X-ray Structural Study. ACS Med Chem Lett, 5, 706-710. PubMed id: 24944748 DOI: 10.1021/ml500101z
Date:
25-Jan-11     Release date:   04-Jan-12    
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

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.27  - 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  

 

 
DOI no: 10.1021/ml500101z ACS Med Chem Lett 5:706-710 (2014)
PubMed id: 24944748  
 
 
Synthesis of Aspartame by Thermolysin: An X-ray Structural Study.
G.Birrane, B.Bhyravbhatla, M.A.Navia.
 
  ABSTRACT  
 
Protease mediated peptide synthesis (PMPS) was first described in the 1930s but remains underexploited today. In most PMPS, the reaction equilibrium is shifted toward synthesis by the aqueous insolubility of product generated. Substrates and proteases are selected by trial and error, yields are modest, and reaction times are slow. Once implemented, however, PMPS reactions can be simple, environmentally benign, and readily scalable to a commercial level. We examined the PMPS of a precursor of the artificial sweetener aspartame, a multiton peptide synthesis catalyzed by the enzyme thermolysin. X-ray structures of thermolysin in complex with aspartame substrates separately, and after PMPS in a crystal, rationalize the reaction's substrate preferences and reveal an unexpected form of substrate inhibition that explains its sluggishness. Structure guided optimization of this and other PMPS reactions could expand the economic viability of commercial peptides beyond current high-potency, low-volume therapeutics, with substantial green chemistry advantages.