1TWW

Dihydropteroate Synthetase, With Bound Substrate Analogue PtPP, From Bacillus anthracis

Summary for 1TWW

• Entry DOI: 10.2210/pdb1tww/pdb
• Related: 1TWS 1TWZ 1TX0 1TX2
• Descriptor: DHPS, Dihydropteroate synthase, SULFATE ION, 6-HYDROXYMETHYLPTERIN-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: anthracis, folate biosynthesis, dihydropteroate, pterine, transferase
• Biological source: Bacillus anthracis
• Total number of polymer chains: 2
• Total formula weight: 67242.22

Authors

Babaoglu, K.,Qi, J.,Lee, R.E.,White, S.W. (deposition date: 2004-07-01, release date: 2004-09-14, Last modification date: 2023-08-23)

Primary citation

Babaoglu, K.,Qi, J.,Lee, R.E.,White, S.W.
Crystal Structure of 7,8-Dihydropteroate Synthase from Bacillus anthracis; Mechanism and Novel Inhibitor Design.
STRUCTURE, 12:1705-1717, 2004

PubMed 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.

PubMed: 15341734
DOI: 10.1016/j.str.2004.07.011

Experimental method

X-RAY DIFFRACTION (2.5 Å)