3NM4

Helicobacter pylori MTAN

Summary for 3NM4

• Entry DOI: 10.2210/pdb3nm4/pdb
• Related: 3NM5 3NM6
• Descriptor: MTA/SAH nucleosidase, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: nucleosidase, hydrolase
• Biological source: Helicobacter pylori (Campylobacter pylori)
• Total number of polymer chains: 2
• Total formula weight: 50594.35

Authors

Ronning, D.R.,Iacopelli, N.M. (deposition date: 2010-06-21, release date: 2010-11-24, Last modification date: 2023-09-06)

Primary citation

Ronning, D.R.,Iacopelli, N.M.,Mishra, V.
Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.
Protein Sci., 19:2498-2510, 2010

PubMed Abstract: The bacterial enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) plays a central role in three essential metabolic pathways in bacteria: methionine salvage, purine salvage, and polyamine biosynthesis. Recently, its role in the pathway that leads to the production of autoinducer II, an important component in quorum-sensing, has garnered much interest. Because of this variety of roles, MTAN is an attractive target for developing new classes of inhibitors that influence bacterial virulence and biofilm formation. To gain insight toward the development of new classes of MTAN inhibitors, the interactions between the Helicobacter pylori-encoded MTAN and its substrates and substrate analogs were probed using X-ray crystallography. The structures of MTAN, an MTAN-Formycin A complex, and an adenine bound form were solved by molecular replacement and refined to 1.7, 1.8, and 1.6 Å, respectively. The ribose-binding site in the MTAN and MTAN-adenine cocrystal structures contain a tris[hydroxymethyl]aminomethane molecule that stabilizes the closed form of the enzyme and displaces a nucleophilic water molecule necessary for catalysis. This research gives insight to the interactions between MTAN and bound ligands that promote closing of the enzyme active site and highlights the potential for designing new classes of MTAN inhibitors using a link/grow or ligand assembly development strategy based on the described H. pylori MTAN crystal structures.

PubMed: 20954236
DOI: 10.1002/pro.524

Experimental method

X-RAY DIFFRACTION (1.7 Å)