1. Department of Plant Biology, Technical University, Spielmannstrasse 7, D-38106 Braunschweig, Germany
2. German Research Center for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany
3. Present address: EMBL Hamburg outstation, DESY, D-22603 Hamburg, Germany

Correspondence to: Günter Schwarz¹ Email: g.schwarz@tu-bs.de

Abstract

The molybdenum cofactor is part of the active site of all molybdenum-dependent enzymes¹, except nitrogenase. The molybdenum cofactor consists of molybdopterin, a phosphorylated pyranopterin², with an ene-dithiolate coordinating molybdenum. The same pyranopterin-based cofactor is involved in metal coordination of the homologous tungsten-containing enzymes found in archea³. The molybdenum cofactor is synthesized by a highly conserved biosynthetic pathway⁴. In plants, the multidomain protein Cnx1 catalyses the insertion of molybdenum into molybdopterin. The Cnx1 G domain (Cnx1G), whose crystal structure has been determined in its apo form, binds molybdopterin with high affinity and participates in the catalysis of molybdenum insertion. Here we present two high-resolution crystal structures of Cnx1G in complex with molybdopterin and with adenylated molybdopterin (molybdopterin–AMP), a mechanistically important intermediate. Molybdopterin–AMP is the reaction product of Cnx1G and is subsequently processed in a magnesium-dependent reaction by the amino-terminal E domain of Cnx1 to yield active molybdenum cofactor. The unexpected identification of copper bound to the molybdopterin dithiolate sulphurs in both structures, coupled with the observed copper inhibition of Cnx1G activity, provides a molecular link between molybdenum and copper metabolism.

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