Essential Elements of Biochemistry BCHM 3050 Dr Srikripa Chandrasekaran Lecture 2 11 15 2 13 15 Notes Nucleic Acids Structure Function of DNA RNA levels structure bonds linkage The structure of DNA was discovered in the 1950s so not too long ago Twisted structure I Levels of Structure in DNA A The structure of DNA can be put into primary secondary and tertiary B The primary structure of DNA consists of the bases C The secondary structure of DNA refers to the double helix twisted D The double helix can be further twisted into super coiling and this is the tertiary structure of DNA II Formation of Phosphodiester Linkage A DNA is deoxyribonucleicacid B The sugar in the second position should not have an OH group C Has 3 phosphate groups that are connected by phosphoanhydride D Phosphoester bond connects an OH group to a phosphate group E The way the chain grows is that nucleotides keep getting added F The 3 OH group is connected to the next sugar by a phosphodiester G Free phosphate group at the 5 OH group becomes involved in a phosphodiester bond the 5 OH group H The very first nucleotide will have a free phosphate group attached to I The very last nucleotide will have a free 3 OH group J The nucleotides in the middle are all involved in phosphodiester linkages phosphodiester linkage 2 phosphoester bonds K We start with a deoxytriphosphate and it loses 2 phosphate groups at the DNA is made If the bases include uracil then the nucleic acid is RNA not DNA L M If the bases include thymine then the nucleic acid is DNA not RNA N For the opposite strand the 3 end is opposite from the 5 end and the 5 end is opposite from the 3 end O Read 5 to 3 start with 5 and end with 3 P Complimentary strands run in opposite directions so they are anti parallel Q A and T are bonded using a double bond R G and C are bonded using a triple bond S The G C bond is harder to break than the A T bond 1 III T DNA is double stranded and the strands are anti parallel meaning that they run in opposite directions U Purine always bonds to a pyrimidine and pyrimidine always bonds to a purine G and C always bond together and A and T always bond together B DNA Spatial Dimensions A B form of DNA is the form characterized by Watson Crick It was originally isolated from aqueous solutions as the partly hydrated sodium salt It is thought that this form represents most native DNA in the cell B Another form the A form is observed when DNA is extracted purified from ethanol which tends to dehydrate the molecule and make it more compact than the B form Also the angle of the base plane with the ribose plane in no longer perpendicular as in B form but tilted 20 degrees away from perpendicular C Major groove is about 2 nm across 1 nm deep This can easily D E F G H I J accommodate a 0 5 nm alpha helix of protein The 2 strands on the double helix are connected by the nitrogenous bases After the 2 strands bond they twist around each other to form a helix The helix has a sugar phosphate backbone and the nitrogenous bases make up the steps inside the helix The B form of DNA is the most common form Anything above 2 nm width can slip a protein inside of it the width of a helix should be wide enough to slip a protein inside of it Alternating groove sizes large small large small etc or major groove minor groove major groove minor groove etc A turn or twist occupies 3 4 nm of helix length and consists of a major groove or a minor groove inside of it About 10 bases can fit in one turn Thus a base occupies about 0 34 nm of helix length K L Four Stabilizing Forces in DNA A Hydrogen bonds IV between A and T and G and C B Hydrophobic interactions forces also helps stabilize it C Van der Waals Forces D Electrostatic Interactions 1 DNA is stabilized by hydrogen bonds between the base pairs 1 Hydrophobic interactions help stabilize DNA so Van der Waals 1 In the backbone the oxygens in the phosphate groups have negative charges which enable electrostatic interactions 2 Because of the charge DNA is soluble in water and can stay in an aqueous environment 3 Water is partially positively charged because of the hydrogens and DNA is partially negatively charged so they can interact 2 V Functions of Major Groove A The function of the major grooves is to attract the proteins and give it B Many of the proteins that interact with DNA are called transcription C Transcription Converting double stranded DNA into single a home factors stranded RNA D Every triplet or 3 bases corresponded to an amino acid and this allows RNA to be made from DNA E Helix turn helix protein motif F Zipper motif a bunch of leucines that open and close a function of the leucines is to separate the double strands of DNA Functions of Minor Groove A These functions are much less known B Drugs are sent to fit into the minor grooves of the DNA C Vitamins and cofactors naturally occupy the minor grooves of DNA DNA Structure A Watson and Crick beat Lymus Polling to the chase when it came to discovering the structure of DNA B 3 forms of DNA B form A form Z form C A form generally forms under dehydrated conditions D Z form has a left handed helix E B form has a right handed helix most common only form that is truly functional VI VII F DNA can adopt the Z form during transcription G Must have perfect dimensions for the Watson and Crick structure in order for the DNA to function VIII Erwin Chargaff Analyzed the Composition of DNA from Several Species A Regardless of what specific type of organism you are all life forms share these same bases in DNA A T G and C B These average numbers continually change C The ratios of A and T are very similar because they bond together D The ratios of G and C are very similar because they bond together E Slight variations in the numbers are likely due to mutations but the variations are so subtle that they are not very significant F Chargaff s Rule 1 2 If an organism has 10 A then it has 10 T If an organism has 10 A then it has 40 G and 40 C because the remaining 80 must be divided by 2 G and C Griffith s Experiment A Griffith isolated 2 different strains of the bacteria R and S B When he mixed the R and S strains they killed the mouse C R was transformed Avery MacLeod McCarty Experiment A They discovered that you could isolate DNA proteins carbohydrates IX X and lipids 3 …
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