2fhs: Difference between revisions
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New page: left|200px<br /><applet load="2fhs" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fhs, resolution 2.70Å" /> '''Structure of Acyl Ca... |
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[[Image:2fhs.gif|left|200px]]<br /><applet load="2fhs" size=" | [[Image:2fhs.gif|left|200px]]<br /><applet load="2fhs" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2fhs, resolution 2.70Å" /> | caption="2fhs, resolution 2.70Å" /> | ||
'''Structure of Acyl Carrier Protein Bound to FabI, the Enoyl Reductase from Escherichia Coli'''<br /> | '''Structure of Acyl Carrier Protein Bound to FabI, the Enoyl Reductase from Escherichia Coli'''<br /> | ||
==Overview== | ==Overview== | ||
Acyl carrier proteins play a central role in metabolism by transporting | Acyl carrier proteins play a central role in metabolism by transporting substrates in a wide variety of pathways including the biosynthesis of fatty acids and polyketides. However, despite their importance, there is a paucity of direct structural information concerning the interaction of ACPs with enzymes in these pathways. Here we report the structure of an acyl-ACP substrate bound to the Escherichia coli fatty acid biosynthesis enoyl reductase enzyme (FabI), based on a combination of x-ray crystallography and molecular dynamics simulation. The structural data are in agreement with kinetic studies on wild-type and mutant FabIs, and reveal that the complex is primarily stabilized by interactions between acidic residues in the ACP helix alpha2 and a patch of basic residues adjacent to the FabI substrate-binding loop. Unexpectedly, the acyl-pantetheine thioester carbonyl is not hydrogen-bonded to Tyr(156), a conserved component of the short chain alcohol dehydrogenase/reductase superfamily active site triad. FabI is a proven target for drug discovery and the present structure provides insight into the molecular determinants that regulate the interaction of ACPs with target proteins. | ||
==About this Structure== | ==About this Structure== | ||
2FHS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Escherichia_coli_042 Escherichia coli 042]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http:// | 2FHS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Escherichia_coli_042 Escherichia coli 042]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FHS OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Rafi, S.]] | [[Category: Rafi, S.]] | ||
[[Category: Simmerling, C.]] | [[Category: Simmerling, C.]] | ||
[[Category: Tonge, P | [[Category: Tonge, P J.]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:21:31 2008'' | ||
