Substrate Interactions with the Nitrogenase Active Site

• Published in: Accounts of chemical research Vol. 38; no. 3; pp. 208 - 214
• Main Authors: Dos Santos, Patricia C, Igarashi, Robert Y, Lee, Hong-In, Hoffman, Brian M, Seefeldt, Lance C, Dean, Dennis R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2005
• Subjects: Alkynes - chemistry; Binding Sites; Electron Spin Resonance Spectroscopy; Models, Molecular; Molecular Structure; Nitrogen - chemistry; Nitrogen Fixation; Nitrogenase - chemistry; Nitrogenase - genetics; Nitrogenase - metabolism; Propanols - chemistry
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/ar040050z

The chemical mechanism for biological cleavage of the N2 triple bond at ambient pressure and temperature has been the subject of intense study for many years. The site of substrate activation and reduction has been localized to a complex cofactor, called FeMo cofactor, yet until now the complexity of the system has denied information concerning exactly where and how substrates interact with the metal−sulfur framework of the active site. In this Account, we describe a combined genetic, biophysical, and biochemical approach that was used to provide direct and detailed information concerning where alternative alkyne substrates interact with FeMo cofactor during catalysis. The relevance and limitations of this work with respect to N2 binding and reduction also are discussed.