Sandbox Reserved 191: Difference between revisions

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OCA, R. Jeremy Johnson, Andrew Bartels, Ryan Mughmaw

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	=Inhibitors of PPT-1=		=Inhibitors of PPT-1=
	'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme, which has a serine [[lipase]] consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF)[https://en.wikipedia.org/wiki/PMSF], a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT-1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT-1. The sulphur of HDSF will <scene name='58/580839/~~Hdsf_bound_to_Ser~~-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a ~~sulfonylation~~ reaction and thus will inhibit the actions of PPT-1.<ref name="INCL">PMID:10801859</ref>		'''<scene name='43/436866/Overall-3-rainbow/1'>PPT-1</scene>''' is a lysosomal enzyme, which has a serine [[lipase]] consensus sequence; a key characteristic of lysosomal enzymes. Despite having a serine lipase consensus sequence, PPT-1, is not deactivated by phenylmethylsulfonyl fluoride (PMSF)[https://en.wikipedia.org/wiki/PMSF], a common serine-modifying reagent. <scene name='58/580839/Hdsf_by_itself/1'>Hexadecylsulfonylfluoride</scene> (HDSF) is a serine-modifying reagent that is able to inhibit the actions of PPT-1 <scene name='58/580839/Basic-hdsf-nosurface/4'>by binding to PPT-1</scene>. Unlike other inhibitors, <scene name='58/580839/Basic-hdsf-surfacelook/2'>HDSF is able to fit in the narrow, hydrophobic groove of PPT-1</scene> leading away from the active site of PPT-1. PMSF is unable to fit into this small narrow groove due to steric constraints that relate to the unique structure of the substrate-binding site of PPT-1. The sulphur of HDSF will <scene name='58/580839/Hdsf_bound_to_ser-115-best/1'>bind to SER-115 in the active site of PPT-1</scene> via a sulponylation reaction and thus will inhibit the actions of PPT-1<ref name="INCL">PMID:10801859</ref>