PDBsum entry 3zot

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Hydrolase PDB id
Protein chain
178 a.a.
BNG ×9
_CL ×2
Waters ×29
PDB id:
Name: Hydrolase
Title: Structure of e.Coli rhomboid protease glpg in complex with monobactam l29 (data set 2)
Structure: Rhomboid protease glpg. Chain: a. Fragment: core tm domain, residues 92-271. Synonym: intramembrane serine protease. Engineered: yes. Other_details: the beta lactam ring is opened by the nucleo attack of s201 on c2-o1 to form a covalent bond
Source: Escherichia coli. Organism_taxid: 469008. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: c41.
2.40Å     R-factor:   0.200     R-free:   0.251
Authors: K.R.Vinothkumar,O.A.Pierrat,J.M.Large,M.Freeman
Key ref: K.R.Vinothkumar et al. (2013). Structure of rhomboid protease in complex with β-lactam inhibitors defines the S2' cavity. Structure, 21, 1051-1058. PubMed id: 23665170 DOI: 10.1016/j.str.2013.03.013
24-Feb-13     Release date:   22-May-13    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P09391  (GLPG_ECOLI) -  Rhomboid protease GlpG
276 a.a.
178 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Rhomboid protease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     serine-type endopeptidase activity     1 term  


DOI no: 10.1016/j.str.2013.03.013 Structure 21:1051-1058 (2013)
PubMed id: 23665170  
Structure of rhomboid protease in complex with β-lactam inhibitors defines the S2' cavity.
K.R.Vinothkumar, O.A.Pierrat, J.M.Large, M.Freeman.
Rhomboids are evolutionarily conserved serine proteases that cleave transmembrane proteins within the membrane. The increasing number of known rhomboid functions in prokaryotes and eukaryotes makes them attractive drug targets. Here, we describe structures of the Escherichia coli rhomboid GlpG in complex with β-lactam inhibitors. The inhibitors form a single bond to the catalytic serine and the carbonyl oxygen of the inhibitor faces away from the oxyanion hole. The hydrophobic N-substituent of β-lactam inhibitors points into a cavity within the enzyme, providing a structural explanation for the specificity of β-lactams on rhomboid proteases. This same cavity probably represents the S2' substrate binding site of GlpG. We suggest that the structural changes in β-lactam inhibitor binding reflect the state of the enzyme at an initial stage of substrate binding to the active site. The structural insights from these enzyme-inhibitor complexes provide a starting point for structure-based design for rhomboid inhibitors.