Journal:JMB:2
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Next, we crystallized <scene name='Journal:JMB:2/Scene_6_2/2'>PON1 in complex with 2-hydroxyquinoline (2HQ)</scene>, which is a lactone analog. As expected, this structure was also <scene name='Journal:JMB:2/Scene_7_2/1'>generally similar to the one at pH 4.5</scene> and <scene name='Journal:JMB:2/Scene_8_2/1'>pH 6.5</scene>. We could now see an <scene name='Journal:JMB:2/Scene_7b_2/1'>active site loop, residues 71-81</scene>, most of which had not been seen at either pH 4.5 or 6.5. The first segment of the active site loop, and <scene name='Journal:JMB:2/Scene_8b_2/1'>residues Y71 and I74 in particular</scene>,comprises part of PON1's active-site wall. Further, 2HQ's carbonyl oxygen and NH moiety <scene name='Journal:JMB:2/Scene_9_2/1'>overlap with the phosphate oxygens</scene> in the apo structure. This overlap supports the notion that both the phosphate ion and 2HQ mimic the binding mode of substrates and/or reaction intermediates. In addition to interacting with the catalytic calcium, 2HQ interacts with the<scene name='Journal:JMB:2/Scene_10_2/1'> side-chains of H115, D269, E53 and N168</scene>. Importantly, while the bound 2HQ is in contact with the <scene name='Journal:JMB:2/Scene_11_2/1'>side-chains of Y71</scene>, in the absence of ligand Y71 is either disordered (pH 6.5), or (pH 4.5) <scene name='Journal:JMB:2/Scene_12_2/1'>positioned outside the binding pocket </scene>. | Next, we crystallized <scene name='Journal:JMB:2/Scene_6_2/2'>PON1 in complex with 2-hydroxyquinoline (2HQ)</scene>, which is a lactone analog. As expected, this structure was also <scene name='Journal:JMB:2/Scene_7_2/1'>generally similar to the one at pH 4.5</scene> and <scene name='Journal:JMB:2/Scene_8_2/1'>pH 6.5</scene>. We could now see an <scene name='Journal:JMB:2/Scene_7b_2/1'>active site loop, residues 71-81</scene>, most of which had not been seen at either pH 4.5 or 6.5. The first segment of the active site loop, and <scene name='Journal:JMB:2/Scene_8b_2/1'>residues Y71 and I74 in particular</scene>,comprises part of PON1's active-site wall. Further, 2HQ's carbonyl oxygen and NH moiety <scene name='Journal:JMB:2/Scene_9_2/1'>overlap with the phosphate oxygens</scene> in the apo structure. This overlap supports the notion that both the phosphate ion and 2HQ mimic the binding mode of substrates and/or reaction intermediates. In addition to interacting with the catalytic calcium, 2HQ interacts with the<scene name='Journal:JMB:2/Scene_10_2/1'> side-chains of H115, D269, E53 and N168</scene>. Importantly, while the bound 2HQ is in contact with the <scene name='Journal:JMB:2/Scene_11_2/1'>side-chains of Y71</scene>, in the absence of ligand Y71 is either disordered (pH 6.5), or (pH 4.5) <scene name='Journal:JMB:2/Scene_12_2/1'>positioned outside the binding pocket </scene>. | ||
| - | '''PDB references:''' Serum paraoxonase-1 by directed evolution at pH 6.5 [[3sre]]; Serum paraoxonase-1 by directed evolution at pH 6.5 in complex with 2-hydroxyquinoline [[3srg]]. | + | '''PDB references:''' Serum paraoxonase-1 by directed evolution at pH 6.5, [[3sre]]; Serum paraoxonase-1 by directed evolution at pH 6.5 in complex with 2-hydroxyquinoline, [[3srg]]. |
</StructureSection> | </StructureSection> | ||
<references/> | <references/> | ||
__NOEDITSECTION__ | __NOEDITSECTION__ | ||
Current revision
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- ↑ Ben-David M, Elias M, Filippi JJ, Dunach E, Silman I, Sussman JL, Tawfik DS. Catalytic Versatility and Backups in Enzyme Active Sites: The Case of Serum Paraoxonase 1. J Mol Biol. 2012 Mar 1. PMID:22387469 doi:10.1016/j.jmb.2012.02.042
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