2fqt
From Proteopedia
(New page: 200px<br /><applet load="2fqt" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fqt, resolution 1.79Å" /> '''Crystal structure of...) |
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| - | [[Image:2fqt.gif|left|200px]]<br /><applet load="2fqt" size=" | + | [[Image:2fqt.gif|left|200px]]<br /><applet load="2fqt" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fqt, resolution 1.79Å" /> | caption="2fqt, resolution 1.79Å" /> | ||
'''Crystal structure of B.subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoyl-propylmercapto]butyric acid'''<br /> | '''Crystal structure of B.subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoyl-propylmercapto]butyric acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether | + | S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2. Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. LuxS utilizes a divalent metal ion as a Lewis acid during catalysis. In this work, a series of structural analogues of the substrate SRH and a 2-ketone intermediate were designed and synthesized. Kinetic studies indicate that the compounds act as reversible, competitive inhibitors against LuxS, with the most potent inhibitors having K(I) values in the submicromolar range. These represent the most potent LuxS inhibitors that have been reported to date. Cocrystal structures of LuxS bound with two of the inhibitors largely confirmed the design principles, i.e., the importance of both the homocysteine and ribose moieties in high-affinity binding to the LuxS active site. |
==About this Structure== | ==About this Structure== | ||
| - | 2FQT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with SO4, CO and H1D as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/S-ribosylhomocysteine_lyase S-ribosylhomocysteine lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.21 4.4.1.21] Full crystallographic information is available from [http:// | + | 2FQT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=CO:'>CO</scene> and <scene name='pdbligand=H1D:'>H1D</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/S-ribosylhomocysteine_lyase S-ribosylhomocysteine lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.21 4.4.1.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FQT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: S-ribosylhomocysteine lyase]] | [[Category: S-ribosylhomocysteine lyase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bell, C | + | [[Category: Bell, C E.]] |
[[Category: Pei, D.]] | [[Category: Pei, D.]] | ||
[[Category: Rajan, R.]] | [[Category: Rajan, R.]] | ||
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[[Category: quorum sensing]] | [[Category: quorum sensing]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:11 2008'' |
Revision as of 15:24, 21 February 2008
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Crystal structure of B.subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoyl-propylmercapto]butyric acid
Overview
S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2. Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. LuxS utilizes a divalent metal ion as a Lewis acid during catalysis. In this work, a series of structural analogues of the substrate SRH and a 2-ketone intermediate were designed and synthesized. Kinetic studies indicate that the compounds act as reversible, competitive inhibitors against LuxS, with the most potent inhibitors having K(I) values in the submicromolar range. These represent the most potent LuxS inhibitors that have been reported to date. Cocrystal structures of LuxS bound with two of the inhibitors largely confirmed the design principles, i.e., the importance of both the homocysteine and ribose moieties in high-affinity binding to the LuxS active site.
About this Structure
2FQT is a Single protein structure of sequence from Bacillus subtilis with , and as ligands. Active as S-ribosylhomocysteine lyase, with EC number 4.4.1.21 Full crystallographic information is available from OCA.
Reference
Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase., Shen G, Rajan R, Zhu J, Bell CE, Pei D, J Med Chem. 2006 May 18;49(10):3003-11. PMID:16686542
Page seeded by OCA on Thu Feb 21 17:24:11 2008
Categories: Bacillus subtilis | S-ribosylhomocysteine lyase | Single protein | Bell, C E. | Pei, D. | Rajan, R. | Shen, G. | Zhu, J. | CO | H1D | SO4 | Luxs | Quorum sensing
