Revision as of 00:23, 27 October 2020

5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase/Pfs

5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (EC 3.2.2.9) (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) and plays a key role in four metabolic processes: biological methylation, polyamine biosynthesis, methionine recycling and bacterial quorum sensing.

H₂O + S-adenosyl-L-homocysteine → adenine + S-(5-deoxy-D-ribose-5-yl)-L-homocysteine

Introduction

Biology

Description of the Pfs

5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (EC 3.2.2.9) cleaves the glycosidic bond of 5’-methylthioadenosine (MTA) and S-adenosylhomocysteine (AdoHcy) to adenine and its corresponding thiol ribose. This hydrolysis reaction is irreversible, with Km=0.43μM and 4.3μM for MTA and AdoHcy, respectively². MTA and AdoHcy are catabolized differently in mammals and microbes¹.

The MTA/AdoHcy nucleosidase active has three separate regions, the purine, ribose, and 5'-alkylthio binding subsites. The three region active site was determined by the presence of adenine and the inhibitors: 5'-methylthio tubercidin (MTT), formycin A (FMA), 5'-methylthio-immucillin A (MT-ImmA), and 5'-methylthio-4'- deoxy-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin A (MTDADMe-ImmA). The structure of MTA/AdoHcy nucleosidase suggests that enzyme is functional as a dimer, with each monomer consisting of a nine-stranded mixed β sheet flanked by six α helices and a small 3₁₀ helix. The nucleosidase has no similarity to any known protein².

References

1. Lee, J. E. et al. Mutational Analysis of a Nucleosidase Involved in Quorum-Sensing Autoinducer-2 Biosynthesis. Biochemistry 44, 11049–11057 (2005).
2. Lee, J. E., Cornell, K. A., Riscoe, M. K. & Howell, P. L. Structure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine Nucleosidase Reveals Similarity to the Purine Nucleoside Phosphorylases. Structure 9, 941–953 (2001).