Sandbox Reserved 955: Difference between revisions

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Instead of the classic scissile bond of the substrate,the hydroxyethylamine moiety 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 situated between the side-chain carboxyl groups of the two active site aspartates within hydrogen bonding distance.

The binding is not symmetric between the two Asp residues : Asp-25 is a little closer than Asp-125. Another aspect of this structure is that only one substituent atom of the Asn-203 side chain makes a polar contact, plus the contact between the hydroxyl group on the tetrahedral carbon and the active site apspartates.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55048/pdf/pnas01047-0128.pdf</ref>

The monomers are directly related to inhibitor binding as this region, <scene name='60/604474/Loop/1'>the loop 49-52</scene>,shows it.The difference between the alpha carbons upon superposition of Gly-49 and Gly-149 is 1.6 A. These loop regions correspond to the extremity of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. As <scene name='60/604474/Loop/3'>the picture</scene>shows, their position are not equivalent because of peptide bond between residues Ile-50 and Gly-51 is turned of 180° compared with Ile-150 and Gly-151 (the symmetrical residues in the other chain.In consequence a direct hydrogen bond between the extremity of the flaps is possible.

The monomers are directly related to inhibitor binding as this region, <scene name='60/604474/Loop/1'>the loop 49-52</scene>,shows it.The difference between the alpha carbons upon superposition of Gly-49 and Gly-149 is 1.6 A. These loop regions correspond to the extremity of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. As <scene name='60/604474/Loop/3'>the picture</scene> shows, their position are not equivalent because of peptide bond between residues Ile-50 and Gly-51 is turned of 180° compared with Ile-150 and Gly-151 (the symmetrical residues in the other chain).In consequence a direct hydrogen bond between the extremity of the flaps is possible.

Sandbox Reserved 955: Difference between revisions

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 Instead of the classic scissile bond of the substrate,the hydroxyethylamine moiety 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 situated between the side-chain carboxyl groups of the two active site aspartates within hydrogen bonding distance.
 The binding is not symmetric between the two Asp residues : Asp-25 is a little closer than Asp-125. Another aspect of this structure is that only one substituent atom of the Asn-203 side chain makes a polar contact, plus the contact between the hydroxyl group on the tetrahedral carbon and the active site apspartates.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55048/pdf/pnas01047-0128.pdf</ref>
-The monomers are directly related to inhibitor binding as this region, <scene name='60/604474/Loop/1'>the loop 49-52</scene>,shows it.The difference between the alpha carbons upon superposition of Gly-49 and  Gly-149 is 1.6 A. These loop regions correspond to the extremity of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. As <scene name='60/604474/Loop/3'>the picture</scene>shows, their position are not equivalent because of peptide bond between residues Ile-50 and Gly-51 is turned of 180° compared with Ile-150 and Gly-151 (the symmetrical residues in the other chain.In consequence a direct hydrogen bond between the extremity of the flaps is possible.
+The monomers are directly related to inhibitor binding as this region, <scene name='60/604474/Loop/1'>the loop 49-52</scene>,shows it.The difference between the alpha carbons upon superposition of Gly-49 and  Gly-149 is 1.6 A. These loop regions correspond to the extremity of the flaps that close over the inhibitor and provide some side-chain contacts to the hydrophobic binding pockets. As <scene name='60/604474/Loop/3'>the picture</scene> shows, their position are not equivalent because of peptide bond between residues Ile-50 and Gly-51 is turned of 180° compared with Ile-150 and Gly-151 (the symmetrical residues in the other chain).In consequence a direct hydrogen bond between the extremity of the flaps is possible.