Potent inhibition of the C-P lyase nucleosidase PhnI by Immucillin-A triphosphate.

Abstract

The C-P lyase complex in bacteria catalyzes the transformation of phosphonates to orthophosphate under conditions of phosphate starvation. The first committed step in the C-P lyase-catalyzed reaction is the displacement of adenine from MgATP by phosphonate substrates, yielding ribose-1-phosphonate-5-triphosphate. In the C-P lyase complex, this reaction is catalyzed by the nucleosidase PhnI and modulated by the addition of PhnG, PhnH, and PhnL. Here we describe the synthesis of Immucillin-A triphosphate, a mimic of the transition state structure for the nucleosidase reaction catalyzed by PhnI. This compound inhibits PhnI with a dissociation constant of 20 nM at pH 7.5.

• Authors: Siddhesh S Kamat, Emmanuel S Burgos, Frank M Raushel
• Journal: Biochemistry (Biochemistry) Vol. 52 Issue 42 Pg. 7366-8 (Oct 22 2013) ISSN: 1520-4995 [Electronic] United States
• PMID: 24111876 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Escherichia coli Proteins
• Organophosphonates
• Pentosephosphates
• Polyphosphates
• Pyrrolidines
• ribose-5-triphosphate
• Adenosine Triphosphate
• Lyases
• carbon-phosphorus lyase
• Magnesium
• Adenine
• Adenosine
• triphosphoric acid
• galidesivir

Topics

• Adenine (analogs & derivatives, pharmacology)
• Adenosine (analogs & derivatives)
• Adenosine Triphosphate (metabolism)
• Catalysis
• Escherichia coli (drug effects, enzymology)
• Escherichia coli Proteins (antagonists & inhibitors, metabolism)
• Lyases (antagonists & inhibitors, metabolism)
• Magnesium (metabolism)
• Models, Chemical
• Organophosphonates (metabolism)
• Pentosephosphates (metabolism)
• Polyphosphates (pharmacology)
• Pyrrolidines (pharmacology)