2jt2
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2jt2.jpg|left|200px]] | [[Image:2jt2.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2jt2", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2jt2| PDB=2jt2 | SCENE= }} | |
| - | | | + | |
| - | | | + | |
| - | }} | + | |
'''Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex''' | '''Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex''' | ||
| Line 29: | Line 26: | ||
[[Category: Raetz, C R.H.]] | [[Category: Raetz, C R.H.]] | ||
[[Category: Zhou, P.]] | [[Category: Zhou, P.]] | ||
| - | [[Category: | + | [[Category: Antibiotic]] |
| - | [[Category: | + | [[Category: Chir-090]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Hydroxamate]] |
| - | [[Category: | + | [[Category: Lipid some]] |
| - | [[Category: | + | [[Category: Lipid a biosynthesis]] |
| - | [[Category: | + | [[Category: Lipid synthesis]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:15:52 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:15, 4 May 2008
Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex
Overview
The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC-CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage.
About this Structure
2JT2 is a Single protein structure of sequence from Aquifex aeolicus. Full crystallographic information is available from OCA.
Reference
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding., Barb AW, Jiang L, Raetz CR, Zhou P, Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. PMID:18025458 Page seeded by OCA on Sun May 4 09:15:52 2008
