3H23: Structural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase

Citation:
Abstract
Dihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis and the target of the sulfonamide class of antibacterials. Resistance and toxicities associated with sulfonamides have led to a decrease in their clinical use. Compounds that bind to the pterin binding site of DHPS, as opposed to the p-amino benzoic acid (pABA) binding site targeted by the sulfonamide agents, are anticipated to bypass sulfonamide resistance. To identify such inhibitors and map the pterin binding pocket, we have performed virtual screening, synthetic, and structural studies using Bacillus anthracis DHPS. Several compounds with inhibitory activity have been identified, and crystal structures have been determined that show how the compounds engage the pterin site. The structural studies identify the key binding elements and have been used to generate a structure-activity based pharmacophore map that will facilitate the development of the next generation of DHPS inhibitors which specifically target the pterin site.
PDB ID: 3H23Download
MMDB ID: 78554
PDB Deposition Date: 2009/4/14
Updated in MMDB: 2009/12
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3H23: dimeric; determined by author and by software (PISA)
Molecular Components in 3H23
Label Count Molecule
Proteins (2 molecules)
2
Dihydropteroate Synthase
Molecule annotation
Chemicals (10 molecules)
1
2
2
8
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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