Sandbox Reserved 321: Difference between revisions

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The reaction takes place as follows. Intially NADH binds to the active site mediated by vander wall interactions with phenylalanine 41 (F41) and interations with lysine 165 <scene name='Sandbox_Reserved_321/Lys165/1'>(K165)</scene><ref name ="Roles of T158"/><ref name ="crystallographic studies"/>. Binding of NADH causes a conformational change in the Aspartate 42 and 43 (E42 and ~~E43~~) side chains and an over all conformational change in InhA<ref name ="crystallographic studies"/>. In addition tyrosine 158 (Y158) playes an important role in alinging the carbonyl substrate, in fact; rotaion about its Cα-Cβ bond by 60° brings it into a position where it can hydrogen bond to the carbonyl of the 2-trans enoyl-ACP and provide it with electrophilic stabalization<ref name ="Roles of T158"/>. Inha then reduces the 2-trans double bond of the substrate by forming a enoyl intermediate through the transfer of a hydride ion from NADH to the thrid carbon of the substrate, followed by protonation of the second carbon<ref name ="crystallographic studies"/>. The biniding of both the substrate and the cofactor induces another conformational change in InhA that allows for the release of the meromycolic acid product<ref name ="crystallographic studies"/>. The meromycolic acids undergo Claisen Condensation with a C26 fatty acid followed by reduction to a mature mycolic acid<ref name ="Fatty Acid Synthesis"/><ref name ="crystallographic studies"/>.

The reaction takes place as follows. Intially NADH binds to the active site mediated by vander wall interactions with phenylalanine 41 (F41) and interations with lysine 165 <scene name='Sandbox_Reserved_321/Lys165/1'>(K165)</scene><ref name ="Roles of T158"/><ref name ="crystallographic studies"/>. Binding of NADH causes a conformational change in the Aspartate 42 and Arginine 43 <scene name='Sandbox_Reserved_321/Asp_42_and_arg_43/1'>(E42 and R43)</scene> side chains and an over all conformational change in InhA<ref name ="crystallographic studies"/>. In addition tyrosine 158 (Y158) playes an important role in alinging the carbonyl substrate, in fact; rotaion about its Cα-Cβ bond by 60° brings it into a position where it can hydrogen bond to the carbonyl of the 2-trans enoyl-ACP and provide it with electrophilic stabalization<ref name ="Roles of T158"/>. Inha then reduces the 2-trans double bond of the substrate by forming a enoyl intermediate through the transfer of a hydride ion from NADH to the thrid carbon of the substrate, followed by protonation of the second carbon<ref name ="crystallographic studies"/>. The biniding of both the substrate and the cofactor induces another conformational change in InhA that allows for the release of the meromycolic acid product<ref name ="crystallographic studies"/>. The meromycolic acids undergo Claisen Condensation with a C26 fatty acid followed by reduction to a mature mycolic acid<ref name ="Fatty Acid Synthesis"/><ref name ="crystallographic studies"/>.

Sandbox Reserved 321: Difference between revisions

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Revision as of 21:18, 1 April 2011 view source Kelly Hrywkiw (talk \| contribs) 155 edits No edit summary ← Older edit		Revision as of 21:30, 1 April 2011 view source Kelly Hrywkiw (talk \| contribs) 155 edits No edit summary Newer edit →
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	The reaction takes place as follows. Intially NADH binds to the active site mediated by vander wall interactions with phenylalanine 41 (F41) and interations with lysine 165 <scene name='Sandbox_Reserved_321/Lys165/1'>(K165)</scene><ref name ="Roles of T158"/><ref name ="crystallographic studies"/>. Binding of NADH causes a conformational change in the Aspartate 42 and 43 (E42 and ~~E43~~) side chains and an over all conformational change in InhA<ref name ="crystallographic studies"/>. In addition tyrosine 158 (Y158) playes an important role in alinging the carbonyl substrate, in fact; rotaion about its Cα-Cβ bond by 60° brings it into a position where it can hydrogen bond to the carbonyl of the 2-trans enoyl-ACP and provide it with electrophilic stabalization<ref name ="Roles of T158"/>. Inha then reduces the 2-trans double bond of the substrate by forming a enoyl intermediate through the transfer of a hydride ion from NADH to the thrid carbon of the substrate, followed by protonation of the second carbon<ref name ="crystallographic studies"/>. The biniding of both the substrate and the cofactor induces another conformational change in InhA that allows for the release of the meromycolic acid product<ref name ="crystallographic studies"/>. The meromycolic acids undergo Claisen Condensation with a C26 fatty acid followed by reduction to a mature mycolic acid<ref name ="Fatty Acid Synthesis"/><ref name ="crystallographic studies"/>.		The reaction takes place as follows. Intially NADH binds to the active site mediated by vander wall interactions with phenylalanine 41 (F41) and interations with lysine 165 <scene name='Sandbox_Reserved_321/Lys165/1'>(K165)</scene><ref name ="Roles of T158"/><ref name ="crystallographic studies"/>. Binding of NADH causes a conformational change in the Aspartate 42 and Arginine 43 <scene name='Sandbox_Reserved_321/Asp_42_and_arg_43/1'>(E42 and R43)</scene> side chains and an over all conformational change in InhA<ref name ="crystallographic studies"/>. In addition tyrosine 158 (Y158) playes an important role in alinging the carbonyl substrate, in fact; rotaion about its Cα-Cβ bond by 60° brings it into a position where it can hydrogen bond to the carbonyl of the 2-trans enoyl-ACP and provide it with electrophilic stabalization<ref name ="Roles of T158"/>. Inha then reduces the 2-trans double bond of the substrate by forming a enoyl intermediate through the transfer of a hydride ion from NADH to the thrid carbon of the substrate, followed by protonation of the second carbon<ref name ="crystallographic studies"/>. The biniding of both the substrate and the cofactor induces another conformational change in InhA that allows for the release of the meromycolic acid product<ref name ="crystallographic studies"/>. The meromycolic acids undergo Claisen Condensation with a C26 fatty acid followed by reduction to a mature mycolic acid<ref name ="Fatty Acid Synthesis"/><ref name ="crystallographic studies"/>.