| Structural highlights
3ann is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 2egh, 1t1r, 1t1s, 1jvs, 3anl, 3anm |
| Gene: | dxr, ispC, yaeM, b0173, JW0168 (Escherichia coli) |
| Activity: | 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Fosmidomycin, a potent inhibitor of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), has antibacterial and antimalaria activity. Due to its poor pharmacokinetics, more lipophilic DXR inhibitors are needed. However, the hydrophobic binding site(s) in DXR remains elusive. Here, pyridine/quinoline containing phosphonates are identified to be DXR inhibitors with IC(50) values as low as 840 nM. We also report three DXR:inhibitor structures, revealing a novel binding mode. The indole group of Trp211 is found to move ~4.6 A to open up a mainly hydrophobic pocket, where the pyridine/quinoline rings of the inhibitors are located and have strong pi-pi stacking/charge-transfer interactions with the indole. Docking studies demonstrate our structures could be used to predict the binding modes of other lipophilic DXR inhibitors. Overall, this work shows an important role of Trp211 in inhibitor recognition and provides a structural basis for future drug design and development.
Structures of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase/Lipophilic Phosphonate Complexes.,Deng L, Endo K, Kato M, Cheng G, Yajima S, Song Y ACS Med Chem Lett. 2011 Feb 10;2(2):165-170. PMID:21379374[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deng L, Endo K, Kato M, Cheng G, Yajima S, Song Y. Structures of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase/Lipophilic Phosphonate Complexes. ACS Med Chem Lett. 2011 Feb 10;2(2):165-170. PMID:21379374 doi:10.1021/ml100243r
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