A. Via et al., Three-dimensional view of the surface motif associated with the P-loop structure: Cis and trans cases of convergent evolution, J MOL BIOL, 303(4), 2000, pp. 455-465
Here we identify the determinants of the nucleotide-binding ability associa
ted with the P-loop-containing proteins, inferring their functional importa
nce from their structural convergence to a unique three-dimensional (3D) mo
tif. (1) A new surface 3D pattern is identified for the P-loop nucleotide-b
inding region, which is more selective than the corresponding sequence patt
ern; (2) the signature displays one residue that we propose is the determin
ant for the guanine-binding ability (the residues aligned to ras D119; this
residue is known to be important only in the G-proteins, we extend the pre
diction to all the other P-loop-containing proteins); and (3) two cases of
convergent evolution at the molecular level are highlighted in the analysis
of the active site: the positive charge aligned to ras K117 and the argini
ne residues aligned to the GAP arginine finger.
The analysis of the residues conserved on protein surfaces allows one to id
entify new functional or evolutionary relationships among protein structure
s that would not be detectable by conventional sequence or structure compar
ison methods. (C), 2000 Academic Press.