Structural analysis of heme proteins: implications for design and prediction
1 Cannon Research Center, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, NC, 28203, USA
2 Department of Biology, University of North Carolina at Charlotte, Charlotte, NC, USA
3 Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
4 Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
5 Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA
Citation and License
BMC Structural Biology 2011, 11:13 doi:10.1186/1472-6807-11-13Published: 3 March 2011
Heme is an essential molecule and plays vital roles in many biological processes. The structural determination of a large number of heme proteins has made it possible to study the detailed chemical and structural properties of heme binding environment. Knowledge of these characteristics can provide valuable guidelines in the design of novel heme proteins and help us predict unknown heme binding proteins.
In this paper, we constructed a non-redundant dataset of 125 heme-binding protein chains and found that these heme proteins encompass at least 31 different structural folds with all-α class as the dominating scaffold. Heme binding pockets are enriched in aromatic and non-polar amino acids with fewer charged residues. The differences between apo and holo forms of heme proteins in terms of the structure and the binding pockets have been investigated. In most cases the proteins undergo small conformational changes upon heme binding. We also examined the CP (cysteine-proline) heme regulatory motifs and demonstrated that the conserved dipeptide has structural implications in protein-heme interactions.
Our analysis revealed that heme binding pockets show special features and that most of the heme proteins undergo small conformational changes after heme binding, suggesting the apo structures can be used for structure-based heme protein prediction and as scaffolds for future heme protein design.