Sandbox Reserved 955: Difference between revisions
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'''Binding site''' | '''Binding site''' | ||
The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate.The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is nestled between the side-chain carboxyl groups of the two active site aspartates within hydrogen bonding distance. The binding is asymmetric with Asp-25 slightly closer than Asp-125. In addition to the contact between the hydroxyl group on the tetrahedral carbon and the active site aspartates, polar contact between inhibitor and enzyme was made through only one substituent atom of the Asn-203 side chain.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55048/pdf/pnas01047-0128.pdf</ref> | The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate.The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is nestled between the side-chain carboxyl groups of the two active site aspartates within hydrogen bonding distance. The binding is asymmetric with Asp-25 slightly closer than Asp-125. In addition to the contact between the hydroxyl group on the tetrahedral carbon and the active site aspartates, polar contact between inhibitor and enzyme was made through only one substituent atom of the Asn-203 side chain.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55048/pdf/pnas01047-0128.pdf</ref> | ||
Monomers appear to be directly related to inhibitor binding. One of these regions is <scene name='60/604474/Loop/1'>the loop 49-52</scene> ; the difference between the alpha carbons upon superposition of Gly-49 and Gly-149 is 1.6 A. These loop regions are the tips of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. The positions of these flaps are not equivalent because the peptide bond between residues <scene name='60/604474/Loop/ | Monomers appear to be directly related to inhibitor binding. One of these regions is <scene name='60/604474/Loop/1'>the loop 49-52</scene> ; the difference between the alpha carbons upon superposition of Gly-49 and Gly-149 is 1.6 A. These loop regions are the tips of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. The positions of these flaps are not equivalent because the peptide bond between residues <scene name='60/604474/Loop/3'>Ile 50 and Gly 51</scene> is turned 1800 compared with that between Ile-150 and Gly-151. This provides a means for a direct hydrogen bond between the tips of the flaps. | ||