1TWS: Dihydropteroate Synthetase From Bacillus Anthracis

Citation:
Abstract
Dihydropterate synthase (DHPS) is the target for the sulfonamide class of antibiotics, but increasing resistance has encouraged the development of new therapeutic agents against this enzyme. One approach is to identify molecules that occupy the pterin binding pocket which is distinct from the pABA binding pocket that binds sulfonamides. Toward this goal, we present five crystal structures of DHPS from Bacillus anthracis, a well-documented bioterrorism agent. Three DHPS structures are already known, but our B. anthracis structures provide new insights into the enzyme mechanism. We show how an arginine side chain mimics the pterin ring in binding within the pterin binding pocket. The structures of two substrate analog complexes and the first structure of a DHPS-product complex offer new insights into the catalytic mechanism and the architecture of the pABA binding pocket. Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine.
PDB ID: 1TWSDownload
MMDB ID: 29485
PDB Deposition Date: 2004/7/1
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1TWS: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1TWS
Label Count Molecule
Proteins (2 molecules)
2
Dhps, Dihydropteroate Synthase
Molecule annotation
Chemicals (12 molecules)
1
12
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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