1t7d
From Proteopedia
(New page: 200px<br /><applet load="1t7d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t7d, resolution 2.47Å" /> '''Crystal structure of...) |
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| - | [[Image:1t7d.gif|left|200px]]<br /><applet load="1t7d" size=" | + | [[Image:1t7d.gif|left|200px]]<br /><applet load="1t7d" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t7d, resolution 2.47Å" /> | caption="1t7d, resolution 2.47Å" /> | ||
'''Crystal structure of Escherichia coli type I signal peptidase in complex with a lipopeptide inhibitor'''<br /> | '''Crystal structure of Escherichia coli type I signal peptidase in complex with a lipopeptide inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We report here the crystallographic and biophysical analysis of a soluble, catalytically active fragment of the Escherichia coli type I signal | + | 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== | ==About this Structure== | ||
| - | 1T7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ARY as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Signal_peptidase_I Signal peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.89 3.4.21.89] Full crystallographic information is available from [http:// | + | 1T7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ARY:'>ARY</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Signal_peptidase_I Signal peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.89 3.4.21.89] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T7D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Signal peptidase I]] | [[Category: Signal peptidase I]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Dalbey, R | + | [[Category: Dalbey, R E.]] |
| - | [[Category: Goodall, J | + | [[Category: Goodall, J J.]] |
[[Category: Kania, M.]] | [[Category: Kania, M.]] | ||
[[Category: Paetzel, M.]] | [[Category: Paetzel, M.]] | ||
| - | [[Category: Page, M | + | [[Category: Page, M G.P.]] |
[[Category: ARY]] | [[Category: ARY]] | ||
[[Category: antibiotic]] | [[Category: antibiotic]] | ||
| Line 32: | Line 32: | ||
[[Category: signal peptide]] | [[Category: signal peptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:43 2008'' |
Revision as of 13:10, 21 February 2008
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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 with as ligand. Active as Signal peptidase I, with EC number 3.4.21.89 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 Feb 21 15:10:43 2008
Categories: 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
