Tw. Traut, THE FUNCTIONS AND CONSENSUS MOTIFS OF 9 TYPES OF PEPTIDE SEGMENTS THAT FORM DIFFERENT TYPES OF NUCLEOTIDE-BINDING SITES, European journal of biochemistry, 222(1), 1994, pp. 9-19
From an analysis of current data on 16 protein structures with defined
nucleotide-binding sites consensus motifs were determined for the pep
tide segments that form such nucleotide-binding sites. This was done b
y using the actual residues shown to contact ligands in the different
protein structures, plus an additional 50 sequences for various kinase
s. Three peptide segments are commonly required to form the binding si
te for ATP or GTP. Binding motif Kinase-1a is found in almost all sequ
ences examined, and functions in binding the phosphates of the ligand.
Variant versions, comparable to Kinase-1a, are found in a subset of p
roteins and appear to be related to unique functions of those enzymes
Motif Kinase-2 contains the conserved aspartate that coordinates the m
etal ion on Mg-ATP. Motif Kinnse-3 occurs in at least four versions, a
nd functions in binding the purine base or the pentose. Two protein st
ructures show ATP-binding at a separate regulatory site, formed by the
motifs Regulatory-1 and Regulatory-2. Structures for adenylate kinase
and guanylate kinase show three different sequence motifs that form t
he binding site for a nucleoside monophosphate (NMP). NMP-1 and NMP-2
bind to the pentose and phosphate of the bound ligand. NMP-1 is found
in almost all the kinases that phosphorylate AMP, CMP, GMP, dTMP, or U
MP. NMP-3a is found in kinases for AMP, GMP, and UMP, while NMP-3b bin
ds only GMP. For the binding of NTPs, three distinct types of nucleoti
de-binding fold structures have been described. Each structure is asso
ciated with a particular function (e.g. transfer of the gamma-phosphat
e, or of the adenylate to an acceptor) and also with a particular spat
ial arrangement of the three Kinase segments evident in the Linear seq
uence for the protein.