NWSGC
North West Structural Genomics Centre

15th August 2005
Daresbury Scientists Reveal Enzyme Mechanism
Understanding enzyme catalysis in the Nitrogen Cycle - crystallography at atomic resolution on NWSGC MAD 10.1 at the SRS

Enzyme_Mechanism.jpgThe nitrogen cycle is a process comparable to photosynthes is in biological significance. Copper containing nitrite reductases are enzymes that perform a crucial catalytic step in this cycle - the conversion on nitrite (NO 2 -) to nitric oxide (NO). This reaction removes nitrogen from the soil and has agronomic, environmental and medical impacts. We used 'crystal harvesting' and substrate-soaking techniques to obtain crystal structures at atomic resolution (0.9, 1.15 and 1.12 ũ of Achromobacter cycloclastes nitrite reductase in its resting state, nitrite-bound and NO-bound forms. In addition, a structure at 1.1 Sresolution revealed the presence of both nitrite and NO at the catalytic type 2 copper centres. The structure of the resting enzyme, measured on the MAD 10.1 beamline, is the highest resolution reported for any copper protein. These structures have provided insights into the process of nitrite reduction, from the initial binding of substrate to the type 2 copper atom, its repositioning prior to catalysis, bond breakage (O-NO) and the formation of a stable NO adduct.

This work reports a collaboration between the Molecular Biophysics Group at Daresbury and the John Innes Centre, Norwich, and is published in the latest volume of the Proceedings of the National Academy of Sciences (USA) : Svetlana Antonyuk, Richard W. Strange, Gary Sawers, Robert R. Eady, S. Samar Hasnain, PNAS, 102 No. 34, 12041-12046, 2005.