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

Zejun Zheng,Alexander Goncearenco,Igor N. Berezovsky

doi:10.1093/nar/gkv1124

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.

Highlights

Nucleotide-containing ligands are indispensable in various biochemical transformations taking place in living cells [1]
We present here a database of 249 profiles of elementary functional loops (EFLs) that are involved in binding of different parts of the 24 most common nucleotide-containing ligands, including mononucleotides formed by nitrogenous bases adenosine, guanosine and cytosine: ATP, AMP, ATP, GMP, GDP, GTP, Cytidine-5 -triphosphate (CTP) and their derivatives PAP, PPS; flavin- and nicotinamidecontaining nucleotides and dinucleotides: FMN, FAD(H), NAD(H), NADP
We believe that the most important advantage of this database stems from the strong theoretical foundation of the EFLs and completeness and the level of detail about interactions of representative EFLs with nucleotidecontaining ligands

Summary

INTRODUCTION

Nucleotide-containing ligands are indispensable in various biochemical transformations taking place in living cells [1]. The set of profiles of EFLs contains several very conserved archetypal signatures, for instance the generalized signatures GxxGxG and GxGxxG of phosphate binding in various nucleotides and dinucleotides, respectively These patterns of glycines expose protein backbone in a particular way so that the main chain amide groups form hydrogen bonds with oxygens in ligand’s phosphate groups. We found strong indications that the most common EFLs with very basic and omnipresent elementary functions are apparently descendants of prebiotic ring-like peptides, which gave rise to the first enzymatic domains in the origin of life [2] Representatives of these EFLs and their evolutionary prototypes [20,21] can be found in different protein families, superfamilies and folds [27], allowing one to unravel deep evolutionary connections in the modern-day protein universe [2]. Is a description of different pages and options available in the database along with a brief note on the implementation and usage

MATERIALS AND METHODS

CONCLUSION