1T7D

Crystal structure of Escherichia coli type I signal peptidase in complex with a lipopeptide inhibitor

Summary for 1T7D

• Entry DOI: 10.2210/pdb1t7d/pdb
• Related: 1B12 1KN9 3IIQ
• Related PRD ID: PRD_000117
• Descriptor: SIGNAL PEPTIDASE I, ARYLOMYCIN A2, 10-METHYLUNDECANOIC ACID, ... (4 entities in total)
• Functional Keywords: signal peptidase, ser/lys dyad, hydrolase, lipopeptide, antibiotic, biaryl bridge, hydrolase-antibiotic complex, hydrolase/antibiotic
• Biological source: ESCHERICHIA COLI; More
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P00803
• Total number of polymer chains: 4
• Total formula weight: 57849.61

Authors

Paetzel, M.,Goodall, J.J.,Kania, M.,Dalbey, R.E.,Page, M.G.P. (deposition date: 2004-05-09, release date: 2004-07-13, Last modification date: 2023-08-23)

Primary citation

Paetzel, M.,Goodall, J.J.,Kania, M.,Dalbey, R.E.,Page, M.G.P.
Crystallographic and Biophysical Analysis of a Bacterial Signal Peptidase in Complex with a Lipopeptide Based Inhibitor.
J.Biol.Chem., 279:30781-, 2004

PubMed Abstract: 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.

PubMed: 15136583
DOI: 10.1074/JBC.M401686200

Experimental method

X-RAY DIFFRACTION (2.47 Å)