4FFS

Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-A

Summary for 4FFS

• Entry DOI: 10.2210/pdb4ffs/pdb
• Descriptor: MTA/SAH nucleosidase, (3R,4S)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(butylsulfanyl)methyl]pyrrolidin-3-ol, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: l-methionine biosynthetic process from s-adenosylmethionine, l-methionine salvage from methylthioadenosine, 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase, adenosylhomocysteine nucleosidase activity, methylthioadenosine nucleosidase activity, hydrolase activity, acting on glycosyl bonds, hydrolase
• Biological source: Helicobacter pylori
• Total number of polymer chains: 1
• Total formula weight: 26657.19

Authors

Haapalainen, A.M.,Rinaldo-Matthis, A.,Brown, R.L.,Norris, G.E.,Almo, S.C.,Schramm, V.L. (deposition date: 2012-06-01, release date: 2012-09-26, Last modification date: 2024-02-28)

Primary citation

Wang, S.,Haapalainen, A.M.,Yan, F.,Du, Q.,Tyler, P.C.,Evans, G.B.,Rinaldo-Matthis, A.,Brown, R.L.,Norris, G.E.,Almo, S.C.,Schramm, V.L.
A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori.
Biochemistry, 51:6892-6894, 2012

PubMed Abstract: Campylobacter and Helicobacter species express a 6-amino-6-deoxyfutalosine N-ribosylhydrolase (HpMTAN) proposed to function in menaquinone synthesis. BuT-DADMe-ImmA is a 36 pM transition state analogue of HpMTAN, and the crystal structure of the enzyme-inhibitor complex reveals the mechanism of inhibition. BuT-DADMe-ImmA has a MIC(90) value of <8 ng/mL for Helicobacter pylori growth but does not cause growth arrest in other common clinical pathogens, thus demonstrating potential as an H. pylori-specific antibiotic.

PubMed: 22891633
DOI: 10.1021/bi3009664

Experimental method

X-RAY DIFFRACTION (1.9 Å)