2o3z

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(New page: 200px<br /><applet load="2o3z" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o3z, resolution 2.25&Aring;" /> '''X-ray crystal struct...)
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[[Image:2o3z.gif|left|200px]]<br /><applet load="2o3z" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2o3z.gif|left|200px]]<br /><applet load="2o3z" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2o3z, resolution 2.25&Aring;" />
caption="2o3z, resolution 2.25&Aring;" />
'''X-ray crystal structure of LpxC complexed with 3-heptyloxybenzoate'''<br />
'''X-ray crystal structure of LpxC complexed with 3-heptyloxybenzoate'''<br />
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==About this Structure==
==About this Structure==
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2O3Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with SO4, ZN, CL and AI7 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2O3Z OCA].
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2O3Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=AI7:'>AI7</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3Z OCA].
==Reference==
==Reference==
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[[Category: lpxc]]
[[Category: lpxc]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 13:03:00 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:24:36 2008''

Revision as of 13:24, 23 January 2008


2o3z, resolution 2.25Å

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X-ray crystal structure of LpxC complexed with 3-heptyloxybenzoate

Overview

The first committed step in lipid A biosynthesis is catalyzed by uridine, diphosphate-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase, (LpxC), a zinc-dependent deacetylase, and inhibitors of LpxC may be useful, in the development of antibacterial agents targeting a broad spectrum of, Gram-negative bacteria. Here, we report the design of amphipathic benzoic, acid derivatives that bind in the hydrophobic tunnel in the active site of, LpxC. The hydrophobic tunnel accounts for the specificity of LpxC toward, substrates and substrate analogues bearing a 3-O-myristoyl substituent., Simple benzoic acid derivatives bearing an aliphatic 'tail' bind in the, hydrophobic tunnel with micromolar affinity despite the lack of a, glucosamine ring like that of the substrate. However, although these, benzoic acid derivatives each contain a negatively charged carboxylate, 'warhead' intended to coordinate to the active site zinc ion, the 2.25A, resolution X-ray crystal structure of LpxC complexed with, 3-(heptyloxy)benzoate reveals 'backward' binding in the hydrophobic, tunnel, such that the benzoate moiety does not coordinate to zinc., Instead, it binds at the outer end of the hydrophobic tunnel., Interestingly, these ligands bind with affinities comparable to those, measured for more complicated substrate analogue inhibitors containing, glucosamine ring analogues and hydroxamate 'warheads' that coordinate to, the active site zinc ion. We conclude that the intermolecular interactions, in the hydrophobic tunnel dominate enzyme affinity in this series of, benzoic acid derivatives.

About this Structure

2O3Z is a Single protein structure of sequence from Aquifex aeolicus with , , and as ligands. Full crystallographic information is available from OCA.

Reference

Amphipathic benzoic acid derivatives: Synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC., Shin H, Gennadios HA, Whittington DA, Christianson DW, Bioorg Med Chem. 2007 Jan 31;. PMID:17296300

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