Nucleotide binding database NBDB – a collection of sequence motifs with specific protein-ligand interactions

Abstract

NBDB database describes protein motifs, elementary functional loops (EFLs) that are involved in binding of nucleotide-containing ligands and other biologically relevant cofactors/coenzymes, including ATP, AMP, ATP, GMP, GDP, GTP, CTP, PAP, PPS, FMN, FAD(H), NAD(H), NADP, cAMP, cGMP, c-di-AMP and c-di-GMP, ThPP, THD, F-420, ACO, CoA, PLP and SAM. The database is freely available online at http://nbdb.bii.a-star.edu.sg. In total, NBDB contains data on 249 motifs that work in interactions with 24 ligands. Sequence profiles of EFL motifs were derived de novo from nonredundant Uniprot proteome sequences. Conserved amino acid residues in the profiles interact specifically with distinct chemical parts of nucleotide-containing ligands, such as nitrogenous bases, phosphate groups, ribose, nicotinamide, and flavin moieties. Each EFL profile in the database is characterized by a pattern of corresponding ligand–protein interactions found in crystallized ligand–protein complexes. NBDB database helps to explore the determinants of nucleotide and cofactor binding in different protein folds and families. NBDB can also detect fragments that match to profiles of particular EFLs in the protein sequence provided by user. Comprehensive information on sequence, structures, and interactions of EFLs with ligands provides a foundation for experimental and computational efforts on design of required protein functions.

Biosynthesis of the nickel-pincer nucleotide cofactor of lactate racemase requires a CTP-dependent cyclometallase

“…11, a and b). Interestingly, the LarC sequence is devoid of known nucleotide-binding motifs according to the nucleotidebinding database (15). We note that the PII signaling transduction proteins of the GlnB-like superfamily also bind a nucleotide, but in that case it is ATP.…”

Simple yet functional phosphate-loop proteins

“…1A). To derive a sequence profile that would represent a prototype of the last common ancestor of this motif, we extended several analyses that identified the β-(P-loop)-α as a primordial motif (20,21,32). Starting with five sequences originally identified by Walker et al (27), we generated a sequence profile and systematically searched the National Center for Biotechnology Information Conserved Domain Database.…”

“…Systematic analyses of contemporary proteins have provided catalogs of ancient motifs, and the so-called Walker-A P-loop is consistently noted in these catalogs (20,21), as are other widely present phosphate-binding loops, including the Rossmann fold's P-loop (22,23). P-loop-containing proteins were also unambiguously assigned to the last universal common ancestor (24)(25)(26).…”

Deciphering common recognition principles of nucleoside mono/di and tri-phosphates binding in diverse proteins via structural matching of their binding sites

“…Sequence motifs such as the kinase‐1 and kinase‐2 motifs specifically for phosphate recognition are also known . Recently, a database called nucleotide binding database (NBDB) has been developed, which contains 63 sequence‐based profiles for ATP and GTP binding, which are typically short sequence stretches, each conserved in individual families of proteins …”

“…6 Recently, a database called nucleotide binding database (NBDB) has been developed, which contains 63 sequence-based profiles for ATP and GTP binding, which are typically short sequence stretches, each conserved in individual families of proteins. 7 One of the first reports of the presence of structural motifs for recognition of nucleotide ligands was that of the four-residue loop that forms two hydrogen bonds with adenine of the ATP ligands bound to cyclic adenosine monophosphate-dependent protein (cAPK) and D-Ala:D-Ala ligase. 8 A supersecondary structure consisting of 103 residues, between cAPK and DD-ligase, has also been reported.…”