Structure and Mechanism of a Eukaryotic FMN Adenylyltransferase

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2009 Apr 21

PMID 19375431

Citations 23

Authors

Carlos Huerta

Dominika Borek

Mischa Machius

Nick V Grishin

Hong Zhang

Affiliations

Soon will be listed here.

Abstract

Flavin mononucleotide adenylyltransferase (FMNAT) catalyzes the formation of the essential flavocoenzyme flavin adenine dinucleotide (FAD) and plays an important role in flavocoenzyme homeostasis regulation. By sequence comparison, bacterial and eukaryotic FMNAT enzymes belong to two different protein superfamilies and apparently utilize different sets of active-site residues to accomplish the same chemistry. Here we report the first structural characterization of a eukaryotic FMNAT from the pathogenic yeast Candida glabrata. Four crystal structures of C. glabrata FMNAT in different complexed forms were determined at 1.20-1.95 A resolutions, capturing the enzyme active-site states prior to and after catalysis. These structures reveal a novel flavin-binding mode and a unique enzyme-bound FAD conformation. Comparison of the bacterial and eukaryotic FMNATs provides a structural basis for understanding the convergent evolution of the same FMNAT activity from different protein ancestors. Structure-based investigation of the kinetic properties of FMNAT should offer insights into the regulatory mechanisms of FAD homeostasis by FMNAT in eukaryotic organisms.

Citing Articles

Identification and characterization of archaeal-type FAD synthase as a novel tractable drug target from the parasitic protozoa .

Wulansari D, Jeelani G, Yazaki E, Nozaki T mSphere. 2024; 9(9):e0034724.

PMID: 39189775 PMC: 11423594. DOI: 10.1128/msphere.00347-24.

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

Dadara A, Nation C, Skelly P BMC Infect Dis. 2024; 24(1):636.

PMID: 38918706 PMC: 11202380. DOI: 10.1186/s12879-024-09538-z.

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke .

Dadara A, Nation C, Skelly P bioRxiv. 2024; .

PMID: 38558993 PMC: 10980065. DOI: 10.1101/2024.03.12.584659.

From Metabolism to Vitality: Uncovering Riboflavin's Importance in Poultry Nutrition.

Shastak Y, Pelletier W Animals (Basel). 2023; 13(22).

PMID: 38003171 PMC: 10668813. DOI: 10.3390/ani13223554.

New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases.

Murgia C, Dehlia A, Guthridge M Nutr Metab (Lond). 2023; 20(1):42.

PMID: 37845732 PMC: 10580530. DOI: 10.1186/s12986-023-00764-x.

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