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What enzymes are regulated?
Enzymes at control points in metabolism Generally the committed step (not necessarily the first step) Note that these are usually essentially irreversible steps
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Aspartate transcarbamylse
3 catalytic clusters (blue and purple) and 3 regulatory clusters (red and yellow) Lehninger 8-24 6 catalytic monomers 6 regulatory monomers
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Aspartate transcarbamylase proves the allosteric concept
6 catalytic monomers 6 regulatory monomers
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Serine proteases Several different families - all have Ser in active site and all have the same reaction mechanism. The two most commonly-studied are: Trypsin family Subtilisin family
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Proteases Proteases of different families break peptide bonds by different mechanisms: metalloproteinases* (carboxypeptidase A) serine proteases* cysteine proteases aspartyl proteases
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Trypsin family of Serine Proteases
Includes: trypsin chymotrypsin (used for numbering) elastase thrombin coagulation enzymes plasmin complement C1r and C1s
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Zymogen activation (Lehninger 8-31)
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Chymotrypsin structure (Lehninger Fig 8-18)
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Specificity pocket explains protease specificity (residues 189, 216 and 226)
Chymotrypsin Trypsin Elastase aromatic basic small, uncharged Diagram from Branden & Tooze, 1991
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