Ligands in PSI structures

Abstract

Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features.

Ligands in crystal structures that aid in functional characterization

“…2). This information, together with an overall structural similarity to a specific class of methyltransferases, suggested a possible catalytic role for this enzyme (Kumar et al, 2010).…”

“…Because the sequence identities for all four proteins are low ($30%), it is unlikely that this homology would have been identified from sequence alignment alone. Kumar et al, 2010). Even unknown ligands (UNLs) can provide mechanistic insights, such as in the uncharacterized protein NP_823353.1 (PDB code 3giw; JCSG, unpublished work), in which the UNL resembles phenylalanine (Fig.…”

“…Interestingly, of the $600 PSI structures identified by the server as proteins lacking functional annotation, about two-thirds have one or more bound ligands which could potentially be used to infer function. For details on how ligands are identified at the JCSG in the course of structure determination, see Kumar et al (2010). For example, Kumar et al (2010) highlight how a bound metal ion (in this case zinc) was instrumental in locating the active sites of three proteins of unknown function: YP_164873.1 (PDB code 3chv; JCSG, unpublished work), YP_555544.1 (PDB code 3e02; JCSG, unpublished work) and YP_556190.1 (PDB code 3e49; JCSG, unpublished work).…”

“…For details on how ligands are identified at the JCSG in the course of structure determination, see Kumar et al (2010). For example, Kumar et al (2010) highlight how a bound metal ion (in this case zinc) was instrumental in locating the active sites of three proteins of unknown function: YP_164873.1 (PDB code 3chv; JCSG, unpublished work), YP_555544.1 (PDB code 3e02; JCSG, unpublished work) and YP_556190.1 (PDB code 3e49; JCSG, unpublished work). Moreover, these proteins were observed to bind zinc in a manner similar to the known 3-keto-5-aminohexanoate cleavage protein (YP_293392.1 from Ralstonia eutropha Jmp123; PDB code 3c6c; JCSG, unpublished work), allowing functional classification (Fig.…”

“…The Protein Structure Initiative (PSI; http://www.nigms.nih.gov/ Initiatives/PSI/) is a significant repository of liganded structures, with the majority (65%) of their 4000+ entries containing bound ligands. Importantly, the Joint Center for Structural Genomics (JCSG; http:// www.jcsg.org) has now developed a publically available search tool, the Ligand Search Server (http://smb.slac.stanford.edu/jcsg/ Ligand_Search/), to mine the entire database of PSI structures for these bound ligands, enabling functional insight into these uncharacterized species (Kumar et al, 2010). Interestingly, of the $600 PSI structures identified by the server as proteins lacking functional annotation, about two-thirds have one or more bound ligands which could potentially be used to infer function.…”