Functional equality in the absence of structural similarity: an added dimension to molecular mimicry.
The crystal structure of meso-tetrasulfonatophenylporphyrin complexed with concanavalin A (ConA) was determined at 1.9 A resolution. Comparison of this structure with that of ConA bound to methyl alpha-d-mannopyranoside provided direct structural evidence of molecular mimicry in the context of ligand receptor binding. The sulfonatophenyl group of meso-tetrasulfonatophenylporphyrin occupies the same binding site on ConA as that of methyl alpha-d-mannopyranoside, a natural ligand. A pair of stacked porphyrin molecules stabilizes the crystal structure by end-to-end cross-linking with ConA resulting in a network similar to that observed upon agglutination of cells by lectins. The porphyrin binds to ConA predominantly through hydrogen bonds and water-mediated interactions. The sandwiched water molecules in the complex play a cementing role, facilitating favorable binding of porphyrin. Seven of the eight hydrogen bonds observed between methyl alpha-d-mannopyranoside and ConA are mimicked by the sulfonatophenyl group of porphyrin after incorporating two water molecules. Thus, the similarity in chemical interactions was manifested in terms of functional mimicry despite the obvious structural dissimilarity between the sugar and the porphyrin.
Goel
M
M
Structural Biology Unit, National Institute of Immunology, New Delhi 110067, India.
Jain
D
D
Kaur
K J
KJ
Kenoth
R
R
Maiya
B G
BG
Swamy
M J
MJ
Salunke
D M
DM
D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D003208:Concanavalin A / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008766:Methylmannosides / Q000737:chemistry; D008958:Models, Molecular; D011166:Porphyrins / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
D008024:Ligands; D008766:Methylmannosides; D011166:Porphyrins; C409084:tetraphenylporphyrin; D003208:Concanavalin A; C008466:methylmannoside