1t7d | pdb_00001t7d
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| 1t7d, resolution 2.47Å | |||||||||||||
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| Ligands: | ARY | ||||||||||||
| Gene: | LEPB (Escherichia coli) | ||||||||||||
| Activity: | Signal peptidase I, with EC number 3.4.21.89 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal structure of Escherichia coli type I signal peptidase in complex with a lipopeptide inhibitor
Overview
We report here the crystallographic and biophysical analysis of a soluble, catalytically active fragment of the Escherichia coli type I signal peptidase (SPase Delta2-75) in complex with arylomycin A2. The 2.5-A resolution structure revealed that the inhibitor is positioned with its COOH-terminal carboxylate oxygen (O45) within hydrogen bonding distance of all the functional groups in the catalytic center of the enzyme (Ser90 O-gamma, Lys145 N-zeta, and Ser88 O-gamma) and that it makes beta-sheet type interactions with the beta-strands that line each side of the binding site. Ligand binding studies, calorimetry, fluorescence spectroscopy, and stopped-flow kinetics were also used to analyze the binding mode of this unique non-covalently bound inhibitor. The crystal structure was solved in the space group P4(3)2(1)2. A detailed comparison is made to the previously published acyl-enzyme inhibitor complex structure (space group: P2(1)2(1)2) and the apo-enzyme structure (space group: P4(1)2(1)2). Together this work provides insights into the binding of pre-protein substrates to signal peptidase and will prove helpful in the development of novel antibiotics.
About this Structure
1T7D is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystallographic and biophysical analysis of a bacterial signal peptidase in complex with a lipopeptide-based inhibitor., Paetzel M, Goodall JJ, Kania M, Dalbey RE, Page MG, J Biol Chem. 2004 Jul 16;279(29):30781-90. Epub 2004 May 10. PMID:15136583
Page seeded by OCA on Thu Mar 20 14:14:46 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Escherichia coli
- Signal peptidase I
- Single protein
- Dalbey, R E.
- Goodall, J J.
- Kania, M.
- Paetzel, M.
- Page, M G.P.
- ARY
- Antibiotic
- Leader peptidase
- Leader peptide
- Lysine general base
- Non-covalently bound inhibitor
- Non-ribosomal peptide synthesis
- Peptide
- Secondary metabolite
- Ser/lys dyad
- Signal peptidase
- Signal peptide
