Molecular Text 3.3

a.       Enzymes must be efficient to avoid __. The rate at which cell metabolism proceeds can be measured by the __
b.      The factor that limits reaction rate is now __; and, the rate will depend on the __
                                                              i.      The cell can increase reaction rates without __ by doing what to form a large protein assembly known as a __; diffusion is then not limited

a.       Another way of increasing metabolic reaction rates is using __, which do what?
b.      Because there are thousands of enzymes that form __, there are __ where different enzymes __; regulation is required at various levels.

                                                              i.      At one level, the cell controls how many molecules of each enzyme it makes by regulating the __
                                                            ii.      The cell controls enzymatic activities by __
                                                          iii.      Enzymes can undergo __
                                                           iv.      __ occurs as well

                                                              i.      The most general process that adjusts reaction rates operates through a direct, reversible change in the __
                                                            ii.      Feedback inhibition: __

1.       A molecule other than the __binds to an enzyme at a special __ outside the active site
2.       It is negative regulation: prevents an enzyme from acting 

                                                              i.      Positive regulation: a regulatory molecule does what?
1.       Occurs when a product in one branch of the metabolic network __

a.       Regulatory molecules often have __totally different from the __of the substrate of the enzyme. It is __
                                                              i.      There is an __ and __ that recognizes the substrates and regulatory molecules, respectively
                                                            ii.      Conformational changes can occur: __ 
b.      The effects of __ on protein follow from a fundamental chemical principle known as __. Whenever two ligands prefer to bind to the __, it follows from basic thermodynamic principles that each ligand must __

                                                              i.      Linkage operates in a negative way if two ligands __. In this case, the binding of the first ligand does what?
b.      A single-subunit enzyme that is regulated by __ can decrease from 90% to 10% activity in response to a 100-fold increase in the concentration of an inhibitory ligand that it binds
                                                              i.      The binding of a molecule of ligand to a single site on one subunit can promote an __ in the entire assembly that helps the neighboring subunits bind the same ligand

1.       As a result, a __ occurs, allowing a relatively small change in __ in the cell to switch the whole assembly from an __ to an __ conformation
b.      Principles involved in a cooperative “__” transition are the same for all proteins

a.       An alternative to the induced fit model is a __, corresponding to __ and __ structures. This is __ between these two states, thereby changing the proportion of active molecules.
b.      __ are begun by __, which has six regulatory and catalytic subunits; __forms two trimers, which face one another and are held by the __

                                                              i.      Binding of catalytic trimers causes an __, allowing __ to __
                                                            ii.      Binding of __ converts the enzymes to the __, from which the __
                                                          iii.      Each regulatory subunit has __, and CTP binding causes the two domains to move relative to each other, causing the__. __ form to stabilize the __

a.       Proteins are regulated by __, such as covalent addition of a phosphate group, which can cause modification in two ways
                                                              i.      Because each phosphate group carries __, the enzyme-catalyzed addition of a phosphate group to a protein can cause a major conformational change in the protein by __, which can affect the __ elsewhere on the protein surface, dramatically changing the protein’s activity. When a second enzyme removes the phosphate group, the protein returns to its original conformation and __

                                                              i.      An attached phosphate group can form part of a structure that the __. As a result, protein __ and __ very often drive the regulated __ and __ of protein complexes

a.       Reversible protein phosphorylation controls the __, __, and __ of both enzymes and many other types of proteins in eukaryotic cells.
b.      Protein phosphorylation involves the __ to the __
                                                              i.      A protein phosphatase catalyzes the __; some are highly specific, whereas others have a broad range of proteins 

a.       The __ belong to a very large family of enzymes; and they have different __ on either end of the __, allowing __of a specific set of proteins it phosphorylates
b.      Rapid addition and removal is important in allowing the phosphorylated proteins to do what?
c.       Many extracellular signals involved in the complex networks of signaling pathways need to be both __ and __ by the cell
                                                              i.      Individual protein kinases serve as __

a.       In general, specific sets of phosphate groups serve to __, while other sets can __. A __ provides a good example as kinases in this class phosphorylate __ and __and are central components of the __ in eukaryotic cells
                                                              i.      Cdk proteins become active as a __ only when bound to a second protein called a __, which is only one of three distinct inputs required to __
1.       In addition to cyclin binding, a __must be added to a specific threonine side chain, and a __elsewhere in the protein must be removed

                                                              i.      Cdk thus monitors a specific set of cell components—a __, __, and __—and acts as an __ that turns on if, and only if, each of these components has attained its appropriate activity state.
                                                            ii.      Sudden destruction of a cyclin immediately does what, and this triggers a specific step in the cell cycle 

a.       The Src family of protien kinases is similar; the Src protein was the first __ to be discovered
                                                              i.      These proteins contain a __ that becomes covalently linked to a __, which does what? After the N-terminal region are the __ and a __, followed by the __.            
                                                   

 i.      They normally exist in an __
1.       Removal  of the__ and the binding of the __ by a specific activating protein turns it on
b.      Protein activity can also be regulated with phosphate attached not to __ but to __

                                                              i.      Hydrolysis of GTP to GDP does what? These are __ and are controlled by __ that determine whether __ or __ is bound
                                                            ii.      There is a large family of __; in each, an important biological activity is controlled by a __that is caused by __ in a __ 

a.       Motor proteins generate forces responsible for __ and the __ and __ of cells. They also power smaller-scale intracellular movements, helping to __, to move __within the cell and to move __ during the synthesis of a new DNA molecule

                                                              i.      They move along tracks by undergoing a series of __ that are __; such movement uses free energy from other sources
1.       To force the entire cycle to proceed in one direction, it is enough to make any change in shape __. Most proteins that can walk in one direction for a long distance achieves this motion by __

a.       ATP hydrolysis releases __; and __ shifts a motor protein from conformation 1 to 2. It is then __, causing conformation 3 to occur. Release of the __ and __ brings about conformation 1. Thus, the cycle is one direction

a.       __ are important membrane-bound pump prtoteins because they function to export __ from the cytoplasm; they are __, with a pair of __ linked to a pair of __ located just below the plasma membrane
b.      __ also exist; an example is __, which uses a proton gradient to produce ATP 

a.       Large proteins with several domains perform more __ than single-domain proteins
                                                              i.      Each of the central processes in a cell is catalyzed by a __
1.       In most such protein machines, an __ drives an ordered series of __ in one or more of the individual protein sububits, enabling the __ to __; allowing enzymes to move directly into position

a.       Protein machines with __parts make efficient use of genetic information, such as SCF ubiquitin ligase, which binds different “__” at different times in the cell cycle
                                                              i.      Specific proteins are targeted for __ in response to specific signals, thereby helping to drive the cell cycle

a.       Proteins are only on when needed. Specific signals allow this. When certain __ bind to receptor proteins in the plasma membrane, they often recruit a set of other proteins to the __ of the plasma membrane to form protein __ that pass the signal on
                                                              i.      Scaffold proteins do what?
                                                           

                                                              i.      Induced proximity explains what?
                                                            ii.      Cells change the locations of their proteins by __ in a variety of different ways, as part of a __, which allows __, thereby __ required for particular reactions in specific regions of the cell

 i.      Scaffolds allow cells to do what?

 Some scaffolds link __ rather than __, __ and causing them to __ with each other in random orientations; this speeds up reactions by creating a __

a.       Aside from phosphorylation, there are other modifications that causes different regulatory events to occur. Each protein’s set of covalent modifications constitutes an important __, which causes a different set of __ as groups are added or removed
b.      __is a term used to describe such research focused on the large-scale analysis of proteins, analogous to the term genomics describing the large-scale analysis of DNA sequences and genes

a.       Biologists map binding interactions in two ways:
                                                              i.      Genetics: __
                                                            ii.      Biochemical: __
b.      Protein interaction maps are useful for identifying the __; they also need to be interpreted with caution because what? Those proteins displaying similar patterns of interactions in two protein interaction maps of crosspecies comparisons are likely to have the same function in the cell