3ZMH

Structure of E.coli rhomboid protease GlpG in complex with monobactam L62


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 

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This is version 1.5 of the entry. See complete history


Literature

Structure of rhomboid protease in complex with beta-lactam inhibitors defines the S2' cavity.

Vinothkumar, K.R.Pierrat, O.A.Large, J.M.Freeman, M.

(2013) Structure 21: 1051-1058

  • DOI: https://doi.org/10.1016/j.str.2013.03.013
  • Primary Citation of Related Structures:  
    3ZMH, 3ZMI, 3ZMJ, 3ZOT

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. vkumar@mrc-lmb.cam.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RHOMBOID PROTEASE GLPG180Escherichia coliMutation(s): 0 
EC: 3.4.21.105
Membrane Entity: Yes 
UniProt
Find proteins for P09391 (Escherichia coli (strain K12))
Explore P09391 
Go to UniProtKB:  P09391
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09391
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BNG
Query on BNG

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A]
nonyl beta-D-glucopyranoside
C15 H30 O6
QFAPUKLCALRPLH-UXXRCYHCSA-N
L62
Query on L62

Download Ideal Coordinates CCD File 
B [auth A]cyclopentyl N-[(1R)-3-oxidanylidene-1-phenyl-propyl]carbamate
C15 H19 N O3
JHRUSYOIALPZLD-CQSZACIVSA-N
78C
Query on 78C

Download Ideal Coordinates CCD File 
C [auth A]CYCLOPENTYL 2-OXO-4-PHENYLAZETIDINE-1-CARBOXYLATE
C15 H17 N O3
HXGULOODWVYRBT-ZDUSSCGKSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
J [auth A],
K [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
L62 PDBBind:  3ZMH IC50: 5267 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.15α = 90
b = 110.15β = 90
c = 128.63γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-22
    Type: Initial release
  • Version 1.1: 2013-05-29
    Changes: Database references
  • Version 1.2: 2013-08-28
    Changes: Database references
  • Version 1.3: 2019-02-27
    Changes: Data collection, Database references, Derived calculations, Experimental preparation, Other
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Other, Structure summary
  • Version 1.5: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary