2vef

Dihydropteroate synthase from Streptococcus pneumoniae

spinqualitylabelsall models 2vef, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vef is a 2 chain structure with sequence from "diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PO4 Related: 2veg Activity: Dihydropteroate synthase, with EC number 2.5.1.15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DHPS_STRR6] DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed DHPS (dihydropteroate synthase) catalyses an essential step in the biosynthesis of folic acid and is the target for the sulfonamide group of antimicrobial drugs. In the present paper we report two crystal structures of DHPS from the respiratory pathogen Streptococcus pneumoniae: the apoenzyme at 1.8 A (1 A=0.1 nm) resolution and a complex with DHPP (6-hydroxymethyl-7,8-dihydropterin monophosphate) at 2.4 A resolution. The enzyme forms a alpha/beta barrel structure, with a highly conserved binding pocket for recognition of the pterin substrate, DHPPP (6-hydroxymethyl-7,8-dihydropterin pyrophosphate). There is a fixed order of substrate binding: DHPPP binds first, followed by the second substrate, pABA (p-aminobenzoic acid). Binding of PP(i) also allows the enzyme to recognize pABA or sulfonamide drugs, which act as pABA analogues. Using equilibrium and pre-steady state kinetic fluorescence measurements, we show that the on-rate for DHPPP binding to the enzyme is relatively low (2.6x10(5) M(-1) x s(-1)) and propose that binding of this substrate induces a large scale movement of the second loop in the enzyme structure to participate in the formation of the pABA-binding site. Two mutations which confer resistance to sulfonamide drugs do not affect DHPPP binding, but have a substantial effect on pABA and sulfonamide recognition. The results show that binding of DHPPP and pABA are separate distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process. Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance.,Levy C, Minnis D, Derrick JP Biochem J. 2008 Jun 1;412(2):379-88. PMID:18321242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydropteroate synthase 3D structures

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