2jt2
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2jt2 |SIZE=350|CAPTION= <scene name='initialview01'>2jt2</scene> | |PDB= 2jt2 |SIZE=350|CAPTION= <scene name='initialview01'>2jt2</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=C90:N-{(1S,2R)-2-HYDROXY-1-[(HYDROXYAMINO)CARBONYL]PROPYL}-4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}BENZAMIDE'>C90</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= lpxC, envA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus]) | |GENE= lpxC, envA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jt2 OCA], [http://www.ebi.ac.uk/pdbsum/2jt2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2jt2 RCSB]</span> | ||
}} | }} | ||
| Line 26: | Line 29: | ||
[[Category: Raetz, C R.H.]] | [[Category: Raetz, C R.H.]] | ||
[[Category: Zhou, P.]] | [[Category: Zhou, P.]] | ||
| - | [[Category: C90]] | ||
| - | [[Category: ZN]] | ||
[[Category: antibiotic]] | [[Category: antibiotic]] | ||
[[Category: chir-090]] | [[Category: chir-090]] | ||
| Line 36: | Line 37: | ||
[[Category: lipid synthesis]] | [[Category: lipid synthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:01:26 2008'' |
Revision as of 01:01, 31 March 2008
| |||||||
| Ligands: | , | ||||||
| Gene: | lpxC, envA (Aquifex aeolicus) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 04:01:26 2008
