DOMAIN CLOSURE IN ADENYLATE KINASE - JOINTS ON EITHER SIDE OF 2 HELICES CLOSE LIKE NEIGHBORING FINGERS

In large variants of adenylate kinase the AMP and ATP substrates are buried by a domain rotating by 90°. Here conformational changes responsible for this domain closure are determined by an analysis of the open state of beef heart mitochondrial adenylate kinase and the closed state of Escherichia coli adenylate kinase. Although these two proteins have sequence differences, the principal structural changes responsible for the domain movements are large, and can clearly be distinguished from the effects of evolution. The mobile domain is linked to the rest of the protein by two helices packed together in an antiparallel fashion. During the closure, deformations take place in four localized regions, called joints, near the N and C termini of these helices. Three of these joints have simple motions that can be well approximated by rotations of three torsion angles, but the joint that makes contact with the ligand involves motion throughout an extended loop: i.e. two torsions on either side of a reverse turn change significantly. The main chain atoms of the joints have few packing constraints. The first pair of joints is responsible for ~30° of the total rotation and the second pair for the remaining 60°. These movements carries along the regions between the joints, the two helices and the rest of the mobile domain to a first approximation, as rigid bodies. This jointed domain closure mechanism is contrasted with the shear mechanisms found in other enzymes. © 1993 Academic Press, Inc.