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

Aspartate transcarbamylse 3 catalytic clusters (blue and purple) and 3 regulatory clusters (red and yellow) Lehninger 8-24 6 catalytic monomers 6 regulatory monomers

Aspartate transcarbamylase proves the allosteric concept 6 catalytic monomers 6 regulatory monomers

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

Proteases Proteases of different families break peptide bonds by different mechanisms: metalloproteinases* (carboxypeptidase A) serine proteases* cysteine proteases aspartyl proteases

Trypsin family of Serine Proteases Includes: trypsin chymotrypsin (used for numbering) elastase thrombin coagulation enzymes plasmin complement C1r and C1s

Zymogen activation (Lehninger 8-31)

Chymotrypsin structure (Lehninger Fig 8-18)

Specificity pocket explains protease specificity (residues 189, 216 and 226) Chymotrypsin Trypsin Elastase aromatic basic small, uncharged Diagram from Branden & Tooze, 1991