4PR3

Crystal structure of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase

Summary for 4PR3

• Entry DOI: 10.2210/pdb4pr3/pdb
• Descriptor: 5'-methylthioadenosine nucleosidase / s-adenosylhomocysteine nucleosidase, ADENINE, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: mixed alpha/beta, hydrolase
• Biological source: Brucella melitensis bv. 1
• Total number of polymer chains: 2
• Total formula weight: 50963.32

Authors

Zhang, X.C.,Kang, X.S.,Zhao, Y.,Jiang, D.H.,Li, X.M.,Chen, Z.L. (deposition date: 2014-03-05, release date: 2014-04-30, Last modification date: 2024-10-30)

Primary citation

Kang, X.S.,Zhao, Y.,Jiang, D.H.,Li, X.M.,Wang, X.P.,Wu, Y.,Chen, Z.L.,Zhang, X.C.
Crystal structure and biochemical studies of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
Biochem.Biophys.Res.Commun., 446:965-970, 2014

PubMed Abstract: The prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH), a process that plays a key role in several metabolic pathways. Its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. Here, we report the crystal structure of BmMTAN in complex with its product adenine at a resolution of 2.6 Å determined by single-wavelength anomalous dispersion method. 11 key residues were mutated for kinetic characterization. Mutations of Tyr134 and Met144 resulted in the largest overall increase in Km, whereas mutagenesis of residues Glu18, Glu145 and Asp168 completely abolished activity. Glu145 and Asp168 were identified as active site residues essential for catalysis. The catalytic mechanism and implications of this structure for broad-based antibiotic design are discussed.

PubMed: 24657441
DOI: 10.1016/j.bbrc.2014.03.045

Experimental method

X-RAY DIFFRACTION (2.606 Å)