1c0r
From Proteopedia
(New page: 200px<br /><applet load="1c0r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c0r, resolution 1.0Å" /> '''COMPLEX OF VANCOMYCIN...) |
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| - | [[Image:1c0r.gif|left|200px]]<br /><applet load="1c0r" size=" | + | [[Image:1c0r.gif|left|200px]]<br /><applet load="1c0r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1c0r, resolution 1.0Å" /> | caption="1c0r, resolution 1.0Å" /> | ||
'''COMPLEX OF VANCOMYCIN WITH D-LACTIC ACID'''<br /> | '''COMPLEX OF VANCOMYCIN WITH D-LACTIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Bacterial resistance to vancomycin has been attributed to the loss of an | + | Bacterial resistance to vancomycin has been attributed to the loss of an intermolecular hydrogen bond between vancomycin and its peptidoglycan target when cell wall biosynthesis proceeds via depsipeptide intermediates rather than the usual polypeptide intermediates. To investigate the relative importance of this hydrogen bond to vancomycin binding, we have determined crystal structures at 1.0 A resolution for the vancomycin complexes with three ligands that mimic peptides and depsipeptides found in vancomycin-sensitive and vancomycin-resistant bacteria: N-acetylglycine, D-lactic acid, and 2-acetoxy-D-propanoic acid. These, in conjunction with structures that have been reported previously, indicate higher-affinity ligands elicit a structural change in the drug not seen with these low-affinity ligands. They also enable us to define a minimal set of drug-ligand interactions necessary to confer higher-affinity binding on a ligand. Most importantly, these structures point to factors in addition to the loss of an intermolecular hydrogen bond that must be invoked to explain the weaker affinity of vancomycin for depsipeptide ligands. These factors are important considerations for the design of vancomycin analogues to overcome vancomycin resistance. |
==About this Structure== | ==About this Structure== | ||
| - | 1C0R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with CL, VAN and LAC as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1C0R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=VAN:'>VAN</scene> and <scene name='pdbligand=LAC:'>LAC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C0R OCA]. |
==Reference== | ==Reference== | ||
Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding., Loll PJ, Kaplan J, Selinsky BS, Axelsen PH, J Med Chem. 1999 Nov 4;42(22):4714-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10579833 10579833] | Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding., Loll PJ, Kaplan J, Selinsky BS, Axelsen PH, J Med Chem. 1999 Nov 4;42(22):4714-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10579833 10579833] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Axelsen, P | + | [[Category: Axelsen, P H.]] |
[[Category: Kaplan, J.]] | [[Category: Kaplan, J.]] | ||
| - | [[Category: Loll, P | + | [[Category: Loll, P J.]] |
[[Category: Selinsky, B.]] | [[Category: Selinsky, B.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: glycopeptide antibiotic]] | [[Category: glycopeptide antibiotic]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:10 2008'' |
Revision as of 10:01, 21 February 2008
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COMPLEX OF VANCOMYCIN WITH D-LACTIC ACID
Overview
Bacterial resistance to vancomycin has been attributed to the loss of an intermolecular hydrogen bond between vancomycin and its peptidoglycan target when cell wall biosynthesis proceeds via depsipeptide intermediates rather than the usual polypeptide intermediates. To investigate the relative importance of this hydrogen bond to vancomycin binding, we have determined crystal structures at 1.0 A resolution for the vancomycin complexes with three ligands that mimic peptides and depsipeptides found in vancomycin-sensitive and vancomycin-resistant bacteria: N-acetylglycine, D-lactic acid, and 2-acetoxy-D-propanoic acid. These, in conjunction with structures that have been reported previously, indicate higher-affinity ligands elicit a structural change in the drug not seen with these low-affinity ligands. They also enable us to define a minimal set of drug-ligand interactions necessary to confer higher-affinity binding on a ligand. Most importantly, these structures point to factors in addition to the loss of an intermolecular hydrogen bond that must be invoked to explain the weaker affinity of vancomycin for depsipeptide ligands. These factors are important considerations for the design of vancomycin analogues to overcome vancomycin resistance.
About this Structure
1C0R is a Protein complex structure of sequences from [1] with , and as ligands. Full crystallographic information is available from OCA.
Reference
Vancomycin binding to low-affinity ligands: delineating a minimum set of interactions necessary for high-affinity binding., Loll PJ, Kaplan J, Selinsky BS, Axelsen PH, J Med Chem. 1999 Nov 4;42(22):4714-9. PMID:10579833
Page seeded by OCA on Thu Feb 21 12:01:10 2008
Categories: Protein complex | Axelsen, P H. | Kaplan, J. | Loll, P J. | Selinsky, B. | CL | LAC | VAN | Glycopeptide antibiotic
