Homologies and anomalies in primary structural patterns of nucleotide binding proteins

Abstract

In searches for homology among nucleotide binding proteins, recent reports have described primary structure alignments for stretches of 30 or so amino acid residues among a variety of proteins including the ray and oncogene products. The significance of these sequence matches has been tested by searching in available data banks for certain conserved residue patterns rcsulting from the alignments. The tests suggest that alignments over these limited stretches are not necessarily justifiable and any implications for residues involved in nucleotide binding must be viewed with caution.With recent advances in the technology of DNA sequencing, the primary structures of many proteins have been elucidated. 'This plethora of data has, probably because of the grcater effort and time required to obtain tertiary structural information, prompted searches for amino acid sequence homologies amongst proteins of known and unknown threedimensional structure. This is particularly so if the various proteins can be related by some common biochemical property. In cases where the sequence matches can be delineated for a 100 or more contiguous residues, with small and few insertions and deletions, the homology would appear significant. For other situations. only a short stretch of 15 to 35 amino acids in length has been reported for proteins consisting of 200 or more amino acids. Arguments for significance in these instances generally center on the alignment of such regions in scveral proteins with similar functions as well as a comparatively high perccntage of amino acid identity which is in the vicinity of 30-40%.Since many proteins bind nucleotides such a s GTP, ADP, or NAD and since conserved marker residues have been identified in the primary, secondary and tertiary structures of NAD-binding dehydrogenases [I ~ 31, there are many examplcs in the recent scientific literature suggesting nucleotide binding regions in proteins through alignment of short scquence spans. The current molecular biology interest in oncogene products has produced a wealth of amino acid scquence data and concomittant attempts to establish functional, structural or possibly evolutionary relationships between these proteins and non-oncogenic proteins of cstablished function and structure. I n this rcport homology studics of oncogene products which possess nucleotide binding properties will be considered: namely, thc rus group of proteins which bind GTP and the src group which bind ATP. By combining alignments from several recent reports through the use of common sequences (e. g. dehydrogenases), particular residue patterns were made salient. Searches of protein sc-

Cloning and nucleic acid sequence of the Salmonella typhimurium pncB gene and structure of nicotinate phosphoribosyltransferase

“…No good fit to this sequence is observed in the primary structure of NAPRTase. For some ATP-utilizing enzymes, a consensus motif (the "flexible loop" [2,12]) that contains the sequence GKT preceded by several small residues was found. Examples from adenylate kinase and RecA are shown in Fig.…”

Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver.

“…-in kinases is also characterized by e residue approximately 14-23 reshe last glycine in the motif (18,26 (19) by screening for mutations that increase the mitotic stability of plasmids whose replication is dependent on weak origins of DNA replication (ARS elements). If the RAR1 protein is involved in sterol biosynthesis, then products derived from the sterol biosynthetic pathway may affect the replication and mitotic stability of plasmids in yeast.…”

“…The deduced protein sequence of mevalonate kinase contains the Gly-Xaa-Gly-Xaa-Xaa-Gly motif, which is present in the nucleotide binding site of protein kinases and many nucleotide binding proteins (18,26). Based on crystallographic studies of the NAD binding region of glyceraldehyde-3-phosphate dehydrogenase, the glycines are required for binding to the ribose moiety in the nucleotide cofactor and for forming a tight turn in the secondary structure between the p-strand and a-helical portions of the molecule (27 (20).…”

Recognition of different nucleotide‐binding sites in primary structures using a property‐pattern approach

“…Distinction of binding sites as described here is impossible with patterns in which only one amino acid appears in one position [37], even by allowing for conservative exchange. Obviously, it is the conservation of obligatory steric and physicochemical properties to which our method is tailored.…”