2z2n
From Proteopedia
(New page: 200px<br /><applet load="2z2n" size="450" color="white" frame="true" align="right" spinBox="true" caption="2z2n, resolution 1.65Å" /> '''Crystal Structure of...) |
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| - | [[Image:2z2n.jpg|left|200px]]<br /><applet load="2z2n" size=" | + | [[Image:2z2n.jpg|left|200px]]<br /><applet load="2z2n" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2z2n, resolution 1.65Å" /> | caption="2z2n, resolution 1.65Å" /> | ||
'''Crystal Structure of selenomethionine substituted virginiamycin B lyase from Staphylococcus aureus'''<br /> | '''Crystal Structure of selenomethionine substituted virginiamycin B lyase from Staphylococcus aureus'''<br /> | ||
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| + | ==Overview== | ||
| + | The streptogramin combination therapy of quinupristin-dalfopristin, (Synercid) is used to treat infections caused by bacterial pathogens, such, as methicillin-resistant Staphylococcus aureus and vancomycin-resistant, Enterococcus faecium. However, the effectiveness of this therapy is being, compromised because of an increased incidence of streptogramin resistance., One of the clinically observed mechanisms of resistance is enzymatic, inactivation of the type B streptogramins, such as quinupristin, by a, streptogramin B lyase, i.e., virginiamycin B lyase (Vgb). The enzyme, catalyzes the linearization of the cyclic antibiotic via a cleavage that, requires a divalent metal ion. Here, we present crystal structures of Vgb, from S. aureus in its apoenzyme form and in complex with quinupristin and, Mg2+ at 1.65- and 2.8-A resolution, respectively. The fold of the enzyme, is that of a seven-bladed beta-propeller, although the sequence reveals no, similarity to other known members of this structural family. Quinupristin, binds to a large depression on the surface of the enzyme, where it, predominantly forms van der Waals interactions. Validated by site-directed, mutagenesis studies, a reaction mechanism is proposed in which the initial, abstraction of a proton is facilitated by a Mg2+ -linked conjugated, system. Analysis of the Vgb-quinupristin structure and comparison with the, complex between quinupristin and its natural target, the 50S ribosomal, subunit, reveals features that can be exploited for developing, streptogramins that are impervious to Vgb-mediated resistance. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Z2N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2Z2N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z2N OCA]. |
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| + | ==Reference== | ||
| + | Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase., Korczynska M, Mukhtar TA, Wright GD, Berghuis AM, Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10388-93. Epub 2007 Jun 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17563376 17563376] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
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[[Category: virginiamycin b lyase]] | [[Category: virginiamycin b lyase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:57:52 2008'' |
Revision as of 09:57, 23 January 2008
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Crystal Structure of selenomethionine substituted virginiamycin B lyase from Staphylococcus aureus
Overview
The streptogramin combination therapy of quinupristin-dalfopristin, (Synercid) is used to treat infections caused by bacterial pathogens, such, as methicillin-resistant Staphylococcus aureus and vancomycin-resistant, Enterococcus faecium. However, the effectiveness of this therapy is being, compromised because of an increased incidence of streptogramin resistance., One of the clinically observed mechanisms of resistance is enzymatic, inactivation of the type B streptogramins, such as quinupristin, by a, streptogramin B lyase, i.e., virginiamycin B lyase (Vgb). The enzyme, catalyzes the linearization of the cyclic antibiotic via a cleavage that, requires a divalent metal ion. Here, we present crystal structures of Vgb, from S. aureus in its apoenzyme form and in complex with quinupristin and, Mg2+ at 1.65- and 2.8-A resolution, respectively. The fold of the enzyme, is that of a seven-bladed beta-propeller, although the sequence reveals no, similarity to other known members of this structural family. Quinupristin, binds to a large depression on the surface of the enzyme, where it, predominantly forms van der Waals interactions. Validated by site-directed, mutagenesis studies, a reaction mechanism is proposed in which the initial, abstraction of a proton is facilitated by a Mg2+ -linked conjugated, system. Analysis of the Vgb-quinupristin structure and comparison with the, complex between quinupristin and its natural target, the 50S ribosomal, subunit, reveals features that can be exploited for developing, streptogramins that are impervious to Vgb-mediated resistance.
About this Structure
2Z2N is a Single protein structure of sequence from Staphylococcus aureus with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase., Korczynska M, Mukhtar TA, Wright GD, Berghuis AM, Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10388-93. Epub 2007 Jun 11. PMID:17563376
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