The two major families of eukaryotic cellular motor ATPases, kinesin and myosin, constitute the myosin-kinesin superfamily within the TRAFAC class of GTPases. The ATPase domain of myosins along with that of the kinesin family of microtubule based motors is believed to have evolved from the core GTPase domain through deletion of strands 6 and 7 and addition of two N-terminal strands [1,2]. Myosins are actin-based motors known or hypothesized to play fundamental roles in many forms of eukaryotic motility such as cell crawling, cytokinesis, phagocytosis, growth cone extension, maintenance of cell shape, and organelle/particle trafficking. Members of the myosin family are biochemically defined as actin-activated Mg(2+)-ATPases. This functionality resides in the ~80 kDa motor domain, almost exclusively found at the N-terminus, which is highly conserved amongst all myosins. The motor domain has been shown to interact with actin, hydrolyze ATP and produce movement in all cases examined to date. The motor domains are relatively conserved with the exception of several surface loops and the amino terminus. In most myosins, the catalytic domain is followed by an α-helical chain-binding region consisting of one or more IQ motifs (see <PDOC50096>). Most myosins also have a C-terminal extension thought to endow class-specific properties such as membrane binding or kinase activity [3,4].

The core myosin motor domain is essentially built of three subdomains connected by flexible linkers (see <PDB:1LKX>). The upper (U50) and lower (L50) 50 kDa subdomain are separated by a cleft which is lined with many conserved residues. The active site with its three highly conserved nucleotide-binding motifs: the P loop, Switch-1, and Switch-2 is located close to the apex of the large cleft and near the interface between the U50 and L50. The third subdomain of the core motor domain is termed the converter region. The converter rectifies and amplifies the structural changes near the active site [5,6,7,8].

The profile we developed covers the entire core myosin motor domain.