1b12
From Proteopedia
(New page: 200px<br /><applet load="1b12" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b12, resolution 1.95Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1b12.gif|left|200px]]<br /><applet load="1b12" size=" | + | [[Image:1b12.gif|left|200px]]<br /><applet load="1b12" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1b12, resolution 1.95Å" /> | caption="1b12, resolution 1.95Å" /> | ||
'''CRYSTAL STRUCTURE OF TYPE 1 SIGNAL PEPTIDASE FROM ESCHERICHIA COLI IN COMPLEX WITH A BETA-LACTAM INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF TYPE 1 SIGNAL PEPTIDASE FROM ESCHERICHIA COLI IN COMPLEX WITH A BETA-LACTAM INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The signal peptidase (SPase) from Escherichia coli is a membrane-bound | + | The signal peptidase (SPase) from Escherichia coli is a membrane-bound endopeptidase with two amino-terminal transmembrane segments and a carboxy-terminal catalytic region which resides in the periplasmic space. SPase functions to release proteins that have been translocated into the inner membrane from the cell interior, by cleaving off their signal peptides. We report here the X-ray crystal structure of a catalytically active soluble fragment of E. coli SPase (SPase delta2-75). We have determined this structure at 1.9 A resolution in a complex with an inhibitor, a beta-lactam (5S,6S penem), which is covalently bound as an acyl-enzyme intermediate to the gamma-oxygen of a serine residue at position 90, demonstrating that this residue acts as the nucleophile in the hydrolytic mechanism of signal-peptide cleavage. The structure is consistent with the use by SPase of Lys 145 as a general base in the activation of the nucleophilic Ser90, explains the specificity requirement at the signal-peptide cleavage site, and reveals a large exposed hydrophobic surface which could be a site for an intimate association with the membrane. As enzymes that are essential for cell viability, bacterial SPases present a feasible antibacterial target: our determination of the SPase structure therefore provides a template for the rational design of antibiotic compounds. |
==About this Structure== | ==About this Structure== | ||
| - | 1B12 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 PO4 and 1PN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.9.21.89 3.9.21.89] Full crystallographic information is available from [http:// | + | 1B12 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=PO4:'>PO4</scene> and <scene name='pdbligand=1PN:'>1PN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.9.21.89 3.9.21.89] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B12 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dalbey, R.]] | [[Category: Dalbey, R.]] | ||
[[Category: Paetzel, M.]] | [[Category: Paetzel, M.]] | ||
| - | [[Category: Strynadka, N | + | [[Category: Strynadka, N C.J.]] |
[[Category: 1PN]] | [[Category: 1PN]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: signal peptide processing]] | [[Category: signal peptide processing]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:50:28 2008'' |
Revision as of 09:50, 21 February 2008
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CRYSTAL STRUCTURE OF TYPE 1 SIGNAL PEPTIDASE FROM ESCHERICHIA COLI IN COMPLEX WITH A BETA-LACTAM INHIBITOR
Overview
The signal peptidase (SPase) from Escherichia coli is a membrane-bound endopeptidase with two amino-terminal transmembrane segments and a carboxy-terminal catalytic region which resides in the periplasmic space. SPase functions to release proteins that have been translocated into the inner membrane from the cell interior, by cleaving off their signal peptides. We report here the X-ray crystal structure of a catalytically active soluble fragment of E. coli SPase (SPase delta2-75). We have determined this structure at 1.9 A resolution in a complex with an inhibitor, a beta-lactam (5S,6S penem), which is covalently bound as an acyl-enzyme intermediate to the gamma-oxygen of a serine residue at position 90, demonstrating that this residue acts as the nucleophile in the hydrolytic mechanism of signal-peptide cleavage. The structure is consistent with the use by SPase of Lys 145 as a general base in the activation of the nucleophilic Ser90, explains the specificity requirement at the signal-peptide cleavage site, and reveals a large exposed hydrophobic surface which could be a site for an intimate association with the membrane. As enzymes that are essential for cell viability, bacterial SPases present a feasible antibacterial target: our determination of the SPase structure therefore provides a template for the rational design of antibiotic compounds.
About this Structure
1B12 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Hydrolase, with EC number 3.9.21.89 Full crystallographic information is available from OCA.
Reference
Crystal structure of a bacterial signal peptidase in complex with a beta-lactam inhibitor., Paetzel M, Dalbey RE, Strynadka NC, Nature. 1998 Nov 12;396(6707):186-90. PMID:9823901
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