A vibrational structure of 7,8-dihydrobiopterin bound to dihydroneopterin aldolase.

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Deng H, Callender R, Dale GE

A vibrational structure of 7,8-dihydrobiopterin bound to dihydroneopterin aldolase.

J Biol Chem. 2000 Sep 29;275(39):30139-43.

PubMed ID

10896664 [ View in PubMed

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Abstract

Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7, 8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin and glycolaldehyde. An inhibitor of the enzyme, 7,8-dihydrobiopterin, free in solution and bound in its complex with the enzyme has been studied by Raman difference spectroscopy. By using isotopically labeled 7,8-dihydrobiopterin and normal mode analyses based on ab initio quantum mechanic methods, we have positively identified some of the Raman bands in the enzyme-bound inhibitor, particularly the important N5=C6 stretch mode. The spectrum of the enzyme-bound inhibitor shows that the pK(a) of N5 is not significantly increased in the complex. This result suggests that N5 of 7,8-dihydroneopterin is not protonated before the bond cleavage of 7,8-dihydroneopterin during the DHNA-catalyzed reaction as has been suggested. Our results also show that the N5=C6 stretch mode of 7, 8-dihydrobiopterin shifts 19 cm(-)(1) upon binding to DHNA. Various possibilities on how the enzyme can bring about such large frequency change of the N5=C6 stretch mode are discussed.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
L-erythro-7,8-dihydrobiopterin	Dihydroneopterin aldolase	Protein	Staphylococcus aureus	Unknown	Not Available	Details