Lipase: Difference between revisions
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== '''Clinical Significance''' == | == '''Clinical Significance''' == | ||
Pancreatic lipase is secreted into the duodenum through the duct system of the pancreas. In a healthy individual, it is at very low concentration in serum. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic cancer, the pancreas may begin to digest itself and release pancreatic enzymes including pancreatic lipase into serum. Measurement of serum concentration of pancreatic lipase can therefore aid in diagnosis of acute pancreatitis.<ref>"Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [http://en.wikipedia.org/wiki/Pancreatic_lipase]</ref>. Due to lipase's activity in the digestion and absorption of fat, there has been a growing market for lipase inhibitors for weight loss pharmaceuticals. The most popular is Orlistat (or Xenical®) which is a natural product from ''Streptomyces toxytricini'' and is the hydrogenation product of lipostation- an irreversible lipase inhibitor. This inhibitor also acts by binding Ser152, producing an ester which hydrolyzes so slow that it is practically irreversible <ref>Kordik, C., Reitz, A. "Pharmacological Treatment of Obesity: Therapeutic Strategies" Journal of Medicinal Chemistry, 1999 (42).</ref>. | Pancreatic lipase is secreted into the duodenum through the duct system of the pancreas. In a healthy individual, it is at very low concentration in serum. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic cancer, the pancreas may begin to digest itself and release pancreatic enzymes including pancreatic lipase into serum. Measurement of serum concentration of pancreatic lipase can therefore aid in diagnosis of acute pancreatitis.<ref>"Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [http://en.wikipedia.org/wiki/Pancreatic_lipase]</ref>. Due to lipase's activity in the digestion and absorption of fat, there has been a growing market for lipase inhibitors for weight loss pharmaceuticals. The most popular is Orlistat (or Xenical®) which is a natural product from ''Streptomyces toxytricini'' and is the hydrogenation product of lipostation- an irreversible lipase inhibitor. This inhibitor also acts by binding Ser152, producing an ester which hydrolyzes so slow that it is practically irreversible <ref>Kordik, C., Reitz, A. "Pharmacological Treatment of Obesity: Therapeutic Strategies" Journal of Medicinal Chemistry, 1999 (42).</ref>. | ||
== 3D Structures of Lipase == | |||
[[Lipase 3D Structures]] | |||
</StructureSection> | </StructureSection> | ||
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**[[2fx5]] – Lip – ''Pseudomonas mendocina''<br /> | **[[2fx5]] – Lip – ''Pseudomonas mendocina''<br /> | ||
**[[1yzf]] – Lip – ''Enterococcus faecalis''<br /> | **[[1yzf]] – Lip – ''Enterococcus faecalis''<br /> | ||
**[[1dt3]], [[1dt5]], [[1dte]], [[1du4]], [[1ein]], [[1tib]], [[4dyh]], [[4ea6]], [[4flf]], [[4gbg]], [[4gwl]], [[4zgb]] - TlLip - ''Thermomyces lanuginose''<br /> | **[[1dt3]], [[1dt5]], [[1dte]], [[1du4]], [[1ein]], [[1tib]], [[4dyh]], [[4ea6]], [[4flf]], [[4gbg]], [[4gwl]], [[4zgb]], [[6hw1]] - TlLip - ''Thermomyces lanuginose''<br /> | ||
**[[5ap9]] – TlLip (mutant)<br /> | **[[5ap9]] – TlLip (mutant)<br /> | ||
**[[1jfr]] – Lip – ''Streptomyces exfoliates''<br /> | **[[1jfr]] – Lip – ''Streptomyces exfoliates''<br /> | ||
**[[5mal]] – Lip – ''Streptomyces rimosus''<br /> | **[[5mal]] – Lip – ''Streptomyces rimosus''<br /> | ||
**[[2lip]] – BcLip – open state<br /> | **[[2lip]] – BcLip – open state<br /> | ||
**[[1cvl]] – Lip – ''Chromobacterium viscosum''<br /> | **[[1cvl]] – Lip – ''Chromobacterium viscosum''<br /> | ||
**[[1tic]] - Lip – ''Rhizopus oryzae''<br /> | **[[1tic]] - Lip – ''Rhizopus oryzae''<br /> | ||
**[[3tgl]], [[4tgl]], [[1tgl]] – RmLip – ''Rhyzomucor miehei''<br /> | **[[3tgl]], [[4tgl]], [[1tgl]], [[6qpp]] – RmLip – ''Rhyzomucor miehei''<br /> | ||
**[[6qpr]] – RmLip (mutant)<br /> | |||
**[[2zvd]] – PsLip - ''Pseudomonas sp.'' – open state<br /> | **[[2zvd]] – PsLip - ''Pseudomonas sp.'' – open state<br /> | ||
**[[2z8x]] - PsLip – extracellular<br /> | **[[2z8x]] - PsLip – extracellular<br /> | ||
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**[[5ce5]] – GtLip (mutant)<br /> | **[[5ce5]] – GtLip (mutant)<br /> | ||
**[[1ji3]], [[1ku0]], [[4fmp]], [[4x6u]] – BstLip – ''Bacillus stearothermophilus''<br /> | **[[1ji3]], [[1ku0]], [[4fmp]], [[4x6u]] – BstLip – ''Bacillus stearothermophilus''<br /> | ||
**[[4x71]], [[4x7b]], [[4x85]] – BstLip (mutant)<br /> | **[[4x71]], [[4x7b]], [[4x85]], [[6s3g]], [[6s3j]], [[6s3v]], [[6fz1]], [[6fz7]], [[6fz8]], [[6fz9]], [[6fza]], [[6fzc]], [[6fzd]] – BstLip (mutant)<br /> | ||
**[[1ah7]] - Lip – ''Bacillus cereus''<br /> | **[[1ah7]] - Lip – ''Bacillus cereus''<br /> | ||
**[[2ory]] – Lip – ''Photobacterium lypoliticum''<br /> | **[[2ory]] – Lip – ''Photobacterium lypoliticum''<br /> | ||
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**[[3guu]] – CaLipA – ''Candida Antarctica''<br /> | **[[3guu]] – CaLipA – ''Candida Antarctica''<br /> | ||
**[[2veo]] – CaLipA – closed state<br /> | **[[2veo]] – CaLipA – closed state<br /> | ||
**[[2qua]], 2qub]] – SmLipA – ''Serratia marcescens''<br /> | **[[2qua]], [[2qub]] – SmLipA – ''Serratia marcescens''<br /> | ||
**[[2qxt]], 2qxu]], 1isp]], 1i6w]], [[5ct4]], [5ct5]], [[5ct6]], [[5cri]] - BsLipA – ''Bacillus subtilis''<br /> | **[[2qxt]], [[2qxu]], [[1isp]], [[1i6w]], [[5ct4]], [[5ct5]], [[5ct6]], [[5cri]] - BsLipA – ''Bacillus subtilis''<br /> | ||
**[[3d2a]], 3d2b]], 3d2c]], 1t2n]], 1t4m]], [[5ct8]], [[5ct9]], [[5cta]], [[5cur]], [[3qzu]], [[3qmm]] - BsLipA (mutant) <br /> | **[[3d2a]], [[3d2b]], [[3d2c]], [[1t2n]], [[1t4m]], [[5ct8]], [[5ct9]], [[5cta]], [[5cur]], [[3qzu]], [[3qmm]] - BsLipA (mutant) <br /> | ||
**[[1r4z]] – BsLipA+Rc-IPG-phosphonate<br /> | **[[1r4z]] – BsLipA+Rc-IPG-phosphonate<br /> | ||
**[[1r50]] – BsLipA +Sc-IPG-phosphonate<br /> | **[[1r50]] – BsLipA +Sc-IPG-phosphonate<br /> | ||
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**[[5gv5]] - CaLipB + phosphonate<br /> | **[[5gv5]] - CaLipB + phosphonate<br /> | ||
**[[3icw]] – CaLipB (mutant) + phosphonate<br /> | **[[3icw]] – CaLipB (mutant) + phosphonate<br /> | ||
**[[5x7k]] – SmLipB NBD <br /><br /> | **[[5x7k]] – SmLipB NBD <br /> | ||
**[[6isp]], [[6isq]], [[6isr]] – LipB (mutant) – ''Pseudozyma antarctica''<br /> | |||
**[[6idy]] - AfLipB - ''Aspergillus fumigatus''<br /> | |||
*Bacterial lipase C | *Bacterial lipase C | ||
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**[[1qz3]] – EaEst2(mutant) (LIPE)+hexadecanesulfonate <br /> | **[[1qz3]] – EaEst2(mutant) (LIPE)+hexadecanesulfonate <br /> | ||
* | *Bile-salt activated lipase | ||
**[[1aql]] – | **[[6h0t]] – hBAL (mutant) <br /> | ||
**[[6h0v]], [[6h18]], [[6h19]], [[6h1a]] – hBAL (mutant) + nerve agent<br /> | |||
**[[1aql]] – bBAL+taurocholate - bovine<br /> | |||
*Monoacylglycerol lipase | *Monoacylglycerol lipase | ||
**[[3hju]], [[3jw8]] - hMAGL <BR /> | |||
**[[3jwe]], [[3pe6]], [[4uuq]], [[6ax1]], [[6bq0]] – hMAGL + inhibitor<br /> | |||
**[[4uuq]] - hMAGLip + SAR <br /> | |||
**[[5zun]] – hMAGL (mutant) + inhibitor<br /> | |||
**[[3rm3]], [[4lhe]], [[5xks]] - BaMAGL – ''Bacillus'' <BR /> | **[[3rm3]], [[4lhe]], [[5xks]] - BaMAGL – ''Bacillus'' <BR /> | ||
**[[3rli]] – BaMAGL + PMSF<br /> | **[[3rli]] – BaMAGL + PMSF<br /> | ||
**[[4ke7]], [[4ke8]], [[4ke9]] – BaMAGL + ligand<br /> | **[[4ke7]], [[4ke8]], [[4ke9]] – BaMAGL + ligand<br /> | ||
**[[4ke6]], [[4kea]] – BaMAGL (mutant) + ligand<br /> | **[[4ke6]], [[4kea]] – BaMAGL (mutant) + ligand<br /> | ||
**[[4zwn]] – yMAGL – yeast<br /> | **[[4zwn]] – yMAGL – yeast<br /> | ||
**[[4zxf]] – yMAGLip + substrate analog<br /> | **[[4zxf]] – yMAGLip + substrate analog<br /> | ||
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**[[4ouk]] - LrE/L (mutant) + inhibitor <br /> | **[[4ouk]] - LrE/L (mutant) + inhibitor <br /> | ||
**[[4bzz]], [[4bzw]] - LpE/L <br /> | **[[4bzz]], [[4bzw]] - LpE/L <br /> | ||
**[[6gup]] - | **[[6gup]] - AfE/L <br /> | ||
**[[1lgy]] – Lip2 – ''Rhizopus niveus''<br /> | **[[1lgy]] – Lip2 – ''Rhizopus niveus''<br /> | ||
**[[1gz7]] - CrLip2 <br /> | **[[1gz7]] - CrLip2 <br /> | ||