Student question of the dayStudent question of the day……..Q1: The number of possible 10mer peptidesis enormous (2010 = ~1013)! Do all of these exist,and if so, how many different functions do theyhave?A: No, they do not all exist. How many do exist?A: No, they do not all exist. How many do exist?Maybe 10Maybe 105 5 different peptides of this size. Thus theredifferent peptides of this size. Thus thereis a lot of is a lot of ““protein spaceprotein space”” that has not been explored. that has not been explored.7.013 Lecture 52.16.07Biochemistry IIIThe cell as a factoryMaterialsManufacturing processPurves 6.3: does a reaction occur spontaneously?!G -ve, spontaneous, releases energy!G +ve, requires energy1Purves 6.8: How fast does a reaction initiate? Transition state 2Purves 6.11: catalysts lower activation energy required for a reactionstablestableTransition stateunstable3Enzyme/substrate specificityPurves 6.10: active site specificity“lock and key” model4An enzyme-catalyzed reaction: Hydrolysis of sucrosesubstrateproducts5The catalytic cycleof sucraseSee Purves 6.106Purves 6.12: how enzymes promote transition stateorientationchargestrain7A tale of one enzyme.....AspPhemethanol8Dietary ProteinPhenylalanine Tyrosinephenylalanine hydroxylasePhenylpyruvic acid CO2, H2OTOXIClow levelsNormal individual9aDietary ProteinPhenylalanine Tyrosinephenylalanine hydroxylasePhenylpyruvic acid CO2, H2OTOXICHIGH LEVELS1/451 amino acids changedArg 408 >> Trpin active sitePhenylketonuric individual9bRegulation of enzyme activityPurves 6.22: pH optima Purves 6.23: temperature optimumPurves Table 6.1: enzyme partnersdihydrofolatetetrahydrofolatedihydrofolate reductaseDi/tetrahydrofolate are required fornucleotide synthesis and DNA modification10AB11Dihyrofolate reductase: target of anticancer drug methotrexate (human)and of antibiotic trimethoprim (bacteria). coenzymesubstrateQuickTime™ and a decompressorare needed to see this picture.QuickTime™ and a decompressorare needed to see this picture.DHFR catalytic cycle: NADP(H), DHF, THF12Sawaya and Kraut, 1997Purves 6.18a: competitive inhibition13GleevecGleevec is acompetitiveinhibitor ofa “leukemiaprotein”14Allosteric regulation of enzyme activitySee also Purves 6.18b, 6.1915Feedback regulationPurves 7.19: feedback in a metabolic pathway16initial substrate/enzymefinal productsIsoleucinesyntheticpathway andfeedbackinhibitionSee Purves 6.2117Enzymes and energy" High energy bondPurves 6.5a:adenosine triphosphate ATP18The ATP cycle (see Purves
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