Biochemistry, 4th Edition P105. Continuing Garrett and Grisham's innovative conceptual and organizing framework, "Essential Questions," BIOCHEMISTRY guides students through course concepts in a way that reveals the beauty and usefulness of biochemistry in the everyday world. Streamlined for increased clarity and readability, this edition also includes new photos and illustrations that show the subject matter consistently throughout the text. New end-of-chapter problems, MCAT practice questions, and the unparalleled text/media integration with the power of CengageNOW round out this exceptional package, giving you the tools you need to both master course concepts and develop critical problem-solving skills you can draw upon. | How Does Protein Degradation Regulate Cellular Levels of Specific Proteins 1003 FIGURE a The complex formed by the E2 enzyme Ubc9 yellow and a target protein RanGAPI blue . b In the Ubc9-RanGAP1 complex the exposed loop of RanGAPI lies in the binding pocket of exposed loop contains the consensus sequence for sumoylation KXD E including Leu525 which is surrounded by hydrophobic residues from Ubc9 Lys526 which is coordinated by Asp127 and Cys93 of Ubc9 and Glu528 which is coordinated by Ubc9 Thr81. The pKa of Lys526 is lowered in this complex activating the lysine amino group for nucleophilic attack to form the SUMO-target protein conjugate. HtrA Proteases Also Function in Protein Quality Control The discussion thus far has stressed the importance of protein quality control to cellular health. HtrA proteases are a class of proteins involved in quality control that combine the dual functions of chaperones and proteasomes. The acronym Htr comes from high temperature requirement because E. coli strains bearing mutations in HtrA genes do not grow at elevated temperatures. In addition to their novel ability to be either chaperones or proteases HtrA proteases are the only known protein quality control factor that is not ATP-dependent. Prokaryotic HtrA proteases act as chaperones at low temperatures 20 C where they have negligible protease activity. However as the temperature increases these proteins switch from a chaperone function to a protease function to remove misfolded or unfolded proteins from the cell. With this functional duality HtrA proteases have the potential to mediate quality control through protein triage see A Deeper Look box on page 1004 . The E. coli HtrA protein DegP is the best characterized HtrA protease. DegP is localized in the E. coli periplasmic space where it oversees quality control of proteins in- I HUMAN BIOCHEMISTRY Proteasome Inhibitors in Cancer Chemotherapy Proteasome inhibition offers a promising approach to treating .
