2bml
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The search for new drugs against Streptococcus pneumoniae (pneumococcus), is driven by the 1.5 million deaths it causes annually. Choline-binding, proteins attach to the pneumococcal cell wall through domains that, recognize choline moieties, and their involvement in pneumococcal, virulence makes them potential targets for drug development. We have, defined chemical criteria involved in the docking of small molecules from, a three-dimensional structural library to the major pneumococcal autolysin, (LytA) choline binding domain. These criteria were used to identify, compounds that could interfere with the attachment of this protein to the, cell wall, and several quinolones that fit this framework were found to, inhibit the cell wall-degrading activity of LytA. Furthermore, these, compounds ... | + | The search for new drugs against Streptococcus pneumoniae (pneumococcus), is driven by the 1.5 million deaths it causes annually. Choline-binding, proteins attach to the pneumococcal cell wall through domains that, recognize choline moieties, and their involvement in pneumococcal, virulence makes them potential targets for drug development. We have, defined chemical criteria involved in the docking of small molecules from, a three-dimensional structural library to the major pneumococcal autolysin, (LytA) choline binding domain. These criteria were used to identify, compounds that could interfere with the attachment of this protein to the, cell wall, and several quinolones that fit this framework were found to, inhibit the cell wall-degrading activity of LytA. Furthermore, these, compounds produced similar effects on other enzymes with different, catalytic activities but that contained a similar choline binding domain;, that is, autolysin (LytC) and the phage lytic enzyme (Cpl-1). Finally, we, resolved the crystal structure of the complex between the choline binding, domain of LytA and ofloxacin at a resolution of 2.6 Angstroms. These data, constitute an important launch pad from which effective drugs to combat, pneumococcal infections can be developed. |
==About this Structure== | ==About this Structure== | ||
| - | 2BML is a | + | 2BML is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae] with SO4, TRS, P6G, XED and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-acetylmuramoyl-L-alanine_amidase N-acetylmuramoyl-L-alanine amidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.28 3.5.1.28] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BML OCA]. |
==Reference== | ==Reference== | ||
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[[Category: ofloxacin-like antibiotics]] | [[Category: ofloxacin-like antibiotics]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:43:53 2007'' |
Revision as of 11:38, 5 November 2007
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OFLOXACIN-LIKE ANTIBIOTICS INHIBIT PNEUMOCOCCAL CELL WALL DEGRADING VIRULENCE FACTORS
Overview
The search for new drugs against Streptococcus pneumoniae (pneumococcus), is driven by the 1.5 million deaths it causes annually. Choline-binding, proteins attach to the pneumococcal cell wall through domains that, recognize choline moieties, and their involvement in pneumococcal, virulence makes them potential targets for drug development. We have, defined chemical criteria involved in the docking of small molecules from, a three-dimensional structural library to the major pneumococcal autolysin, (LytA) choline binding domain. These criteria were used to identify, compounds that could interfere with the attachment of this protein to the, cell wall, and several quinolones that fit this framework were found to, inhibit the cell wall-degrading activity of LytA. Furthermore, these, compounds produced similar effects on other enzymes with different, catalytic activities but that contained a similar choline binding domain;, that is, autolysin (LytC) and the phage lytic enzyme (Cpl-1). Finally, we, resolved the crystal structure of the complex between the choline binding, domain of LytA and ofloxacin at a resolution of 2.6 Angstroms. These data, constitute an important launch pad from which effective drugs to combat, pneumococcal infections can be developed.
About this Structure
2BML is a Single protein structure of sequence from Streptococcus pneumoniae with SO4, TRS, P6G, XED and PG4 as ligands. Active as N-acetylmuramoyl-L-alanine amidase, with EC number 3.5.1.28 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Ofloxacin-like antibiotics inhibit pneumococcal cell wall-degrading virulence factors., Fernandez-Tornero C, Garcia E, de Pascual-Teresa B, Lopez R, Gimenez-Gallego G, Romero A, J Biol Chem. 2005 May 20;280(20):19948-57. Epub 2005 Mar 15. PMID:15769740
Page seeded by OCA on Mon Nov 5 13:43:53 2007
Categories: N-acetylmuramoyl-L-alanine amidase | Single protein | Streptococcus pneumoniae | Fernandez-Tornero, C. | Garcia, E. | Gimenez-Gallego, G. | Lopez, R. | Pascual-Teresa, B.D. | Romero, A. | P6G | PG4 | SO4 | TRS | XED | Cell wall attachment | Choline-binding domain | Ofloxacin-like antibiotics
