I. Introduction
Ricin, a toxic glycoprotein produced by the plant Ricinus comunis, is a type II RIP (ribosome inactivating protein) which consists of two smaller proteins covalently bonded by a disulfide bridge. These two proteins are the A chain (RTA) and the B chain (RTB).
RTA is an N-glycosidase, which removes the bases from nucleic acids like DNA or RNA. RTA specifically targets a sequence in ribosomal RNA (the GAGA tetraloop of 28S rRNA) which completely inactivates the ribosomes. Without functional ribosomes, the cell cannot produce the enzymes it needs to operate and dies.
RTB is a lectin (a protein which binds to sugar) which recognizes a galactose containing receptor on the surface of cells. Most proteins on the outsides of cells are decorated by complex sugar chains, several of which contain galactose. Beside attaching to the outside of cells, RTB can attach itself to proteins as they are internalized into the cell.
During the internaliztion process, the disulfide bond is cleaved and ricin separates into the A and B chain.
II. Structural Features of Ricin
Primary Structures:
Secondary Structure:
III. Binding Regions
Ricin A-chain is an N-glycosidase that hydrolyzes the adenine ring from a specific adenosine of rRNA. The formycin ring stacks between Tyr80 and Tyr123 while forming H-bonds with the carbonyl group and amido nitrogen atom of Val81 and with the carbonyl group of Gly121.
A. Formycin Monophospahte
B. Pteroic Acid
Pteroic acid has been identified as an inhibitor of Ridin wiht a Ki of .6mM. The pterin ring displaces Tyr80 and binds making specific hydrogen bonds to active site residues. The benzoate group of pteroic acid binds on the opposite side of Tyr80 creating van der Waals interations with the Tyr ring and forming a H-bond with Asn 78. H-bonds are also formed with Gly121, Arg180, and Val81.
C. Neopterin
Neopterin, a propane triol derivative of pterin also demonstarted inhibitory effects on ricin.
IV. Molecular Properites
The following properites are for the Ricin A-chain and Formycin Monophosphate Complex.
Curvature
The local curvature at each surface point (or vertex) is calculated. The curvature values can then be used to color-code the surface. The default coloring scheme is displayed above with negative curvature denoting a concave surface patch (black) and positive denoting a convex surface patch (green). White surface patches denotes zero curvature surface patches.
Electrostatic potential
The electrostatic potential is calculated around the molecules selected using GRASP's built-in Finite Difference Poisson Boltzmann solver. This potential can then be used to color-code the molecular graphics generated. The default coloring scheme is displayed above with negative potential color- coded in red, and positive potential color-coded in blue. Only the the charges on the selected macromolecules and ions are included in the electrostatic potential calculations.
Hydrophobicity
Hydrophobicity by atom type: Here, aliphatic and aromatic carbon atoms and sulfur atoms are considered hydrophobic while nitrogen, oxygen and charged carbon atoms are considered polar. The default coloring scheme is displayed above with property values of 0 denoting polar character (yellow) and 1.0 denoting hydrophobic character (gray).
Amino acid sequence variability:
Amino acid sequence variability within the protein family is obtained from the HSSP database of sequence alignments. The metric plotted is the 'Relative Entropy' at an amino acid position in the sequence. This number ranges from 0 (completely conserved) to 100 (completely variable). The default coloring scheme is displayed above with property values ranging from 0.0 (dark orange) to 80.0 (white). The reliability of this measure of sequence variability depends on the number and degree of similarity of the sequences used in the alignment.
References
Gluck, A., Wool, I. (1996). Determination of th 28 S ribosomal RNA identity element (G4319) for alpha -sarcin and the relationshipon of recognition to the selection of the catalytic site. J. Mol. Bio. 256, 838-848.
Xinjian, Y. , Hollis, T., Svinth, M., Day, P., Monzingo, A., Milne, G., & Robertus, J. (1997). Structure-based identification of a ricin inhibitor. J. Mol. Bio. 266, 1043-1049.
http://www.oikos.warwick.ac.uk/~biojo/work/ricin.html
http://medinfo.wustl.edu/~ysp/MSN/posts/archives/mar97/856891268.Bc.r.html
http://www.rcsb.org/pdb/cgi/explore.cgi?pid=28416957227407&pdbId=2AAI
http://jsdnt.claremont.edu/biochem98/ricin/ricin.htm
http://trantor.bioc.columbia.edu/GRASS/surfserv_picgallery.cgi?1fmp