4PR3: Crystal Structure Of Brucella Melitensis 5'-methylthioadenosine/s- Adenosylhomocysteine Nucleosidase

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 2.6A 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.
PDB ID: 4PR3Download
MMDB ID: 119803
PDB Deposition Date: 2014/3/5
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2.61  Å
Source Organism:
Similar Structures:
Biological Unit for 4PR3: dimeric; determined by author and by software (PISA)
Molecular Components in 4PR3
Label Count Molecule
Proteins (2 molecules)
5'-methylthioadenosine Nucleosidase / S- Adenosylhomocysteine Nucleosidase
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB