Dataset Information

Structural differences between Pb2+- and Ca2+-binding sites in proteins: implications with respect to toxicity.

ABSTRACT: Pb(2+) is known to displace physiologically-relevant metal ions in proteins. To investigate potential relationships between Pb(2+)/protein complexes and toxicity, data from the protein data bank were analyzed to compare structural properties of Pb(2+)- and Ca(2+)-binding sites. Results of this analysis reveal that the majority of Pb(2+) sites (77.1%) involve 2-5 binding ligands, compared with 6+/-2 for non-EF-Hand and 7+/-1 for EF-Hand Ca(2+)-binding sites. The mean net negative charge by site (1.7) fell between values noted for non-EF-Hand (1+/-1) and EF-Hand (3+/-1). Oxygen is the dominant ligand for both Pb(2+) and Ca(2+), but Pb(2+) binds predominantly with sidechain Glu (38.4%), which is less prevalent in both non-EF-Hand (10.4%) and EF-Hand (26.6%) Ca(2+)-binding sites. A comparison of binding geometries where Pb(2+) has replaced Ca(2+) in calmodulin (CaM) and Zn(2+) in 5-aminolaevulinic acid dehydratase (ALAD) revealed protein structural changes that appear to be unrelated to ionic displacement. Structural changes observed with CaM may be related to opportunistic binding of Pb(2+) in regions of high electrostatic charge, whereas ALAD may bind multiple Pb(2+) ions in the active site. These results suggest that Pb(2+) adapts to structurally-diverse binding geometries and that opportunistic binding may play an active role in molecular metal toxicity.

SUBMITTER: Kirberger M

PROVIDER: S-EPMC2567809 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structural differences between Pb2+- and Ca2+-binding sites in proteins: implications with respect to toxicity.

Kirberger Michael M Yang Jenny J JJ

Journal of inorganic biochemistry 20080705 10

Pb(2+) is known to displace physiologically-relevant metal ions in proteins. To investigate potential relationships between Pb(2+)/protein complexes and toxicity, data from the protein data bank were analyzed to compare structural properties of Pb(2+)- and Ca(2+)-binding sites. Results of this analysis reveal that the majority of Pb(2+) sites (77.1%) involve 2-5 binding ligands, compared with 6+/-2 for non-EF-Hand and 7+/-1 for EF-Hand Ca(2+)-binding sites. The mean net negative charge by site ( ...[more]

PMID: 18684507

Similar Datasets

Project description:Ca(2+)-binding sites in proteins exhibit a wide range of polygonal geometries that directly relate to an equally-diverse set of biological functions. Although the highly-conserved EF-Hand motif has been studied extensively, non-EF-Hand sites exhibit much more structural diversity which has inhibited efforts to determine the precise location of Ca(2+)-binding sites, especially for sites with few coordinating ligands. Previously, we established an algorithm capable of predicting Ca(2+)-binding sites using graph theory to identify oxygen clusters comprised of four atoms lying on a sphere of specified radius, the center of which was the predicted calcium position. Here we describe a new algorithm, MUG (MUltiple Geometries), which predicts Ca(2+)-binding sites in proteins with atomic resolution. After first identifying all the possible oxygen clusters by finding maximal cliques, a calcium center (CC) for each cluster, corresponding to the potential Ca(2+) position, is located to maximally regularize the structure of the (cluster, CC) pair. The structure is then inspected by geometric filters. An unqualified (cluster, CC) pair is further handled by recursively removing oxygen atoms and relocating the CC until its structure is either qualified or contains fewer than four ligand atoms. Ligand coordination is then determined for qualified structures. This algorithm, which predicts both Ca(2+) positions and ligand groups, has been shown to successfully predict over 90% of the documented Ca(2+)-binding sites in three datasets of highly-diversified protein structures with 0.22 to 0.49 A accuracy. All multiple-binding sites (i.e. sites with a single ligand atom associated with multiple calcium ions) were predicted, as were half of the low-coordination sites (i.e. sites with less than four protein ligand atoms) and 14/16 cofactor-coordinating sites. Additionally, this algorithm has the flexibility to incorporate surface water molecules and protein cofactors to further improve the prediction for low-coordination and cofactor-coordinating Ca(2+)-binding sites.

Dataset Information

Structural differences between Pb2+- and Ca2+-binding sites in proteins: implications with respect to toxicity.

Publications

Structural differences between Pb2+- and Ca2+-binding sites in proteins: implications with respect to toxicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets