ELEMENTS OF BIOL CHEM
ELEMENTS OF BIOL CHEM BICH 303
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This 31 page Class Notes was uploaded by Ceasar Fritsch on Wednesday October 21, 2015. The Class Notes belongs to BICH 303 at Texas A&M University taught by Timothy Devarenne in Fall. Since its upload, it has received 35 views. For similar materials see /class/225849/bich-303-texas-a-m-university in Biochemistry at Texas A&M University.
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Date Created: 10/21/15
Genetic transfer of information Nucleic acids Where does the information come from to produce proteins DNA is hereditary molecule in all cellular life forms RNA mediates translation of DNA information to make proteins DNA sequence bases dictates protein sequence DNA 3 km of DNA in a single nucleus Deoxyribonucleic ACid overall DNA structure very complex interaction with proteins coiling coiling of coil allows for packing of huge amounts of DNA into small area double helix structure i 2005 Brwkscwe mum DNA Structure double helix structure jaq History Gregor Mendel Austrian priest and scientist 1856 1853 discovered the inheritance oftraits follow laws Mendelian genetics using pea plants his work not fully appreciated until 1900 Friedrich Miescher Swiss physician worked at University of Tubingen Germany 1869 discovered DNA in pus on discarded surgical bandages found it in nucleus and called it nuclein Phoebus Levene Russian born worked at Rockefeller Institute of Medical Research 1919 identified the base sugar and phosphate nucleotide unit of DNA Alfred Hershey and Martha Chase 1953 confirmed DNA as hereditary genetic material DNA Structure double helix structure James D Watson and Francis Crick History Watson American Crick English I Worked at University of Cambridge 1 1953 determined the double helix structure of DNA Controversially they used the DNA xray diffraction images of Rosalind Franklin Kings College London with out her permission 1957 Crick presented the Central 1 Dogma that laid out frame work quot of DNA to RNA to protein laying the foundation of modern molecula biology 1962 Watson and Crick awarded Nobel Prize in Physiology or Medicine DNA Structure History James Watson in 1988 initiated the Human Genome Project lead project until 1992 May 31 2007 became the second person to have his full genome sequence publishe Jim Watson LDL Recegtor Gene DNA Structure double helix structure Two polynucleotide chains in a helix Each polynucleotide chain made up of backbone sugar ribose and phosphate P04 monomer units as with proteins DNA is made up of monomer units nucleotides DNA Structure double helix structure Nucleotide bases made up of a nucleic acid ribose sugar and a phosphate base refers to a ring structure not as in pH Nuclelc acuds NIHZ ltHgt H H I I 1 H 1 NfTCI I Nf ch HN frz HNf ch Pyrlmldlnes smgIermg IICI UH It ItII HH r UH r I t f A r f l I I aromatic compound N 0 g 0 g 0 NY Pyrimidine Mosine Thynline Uracil in DNA amp RNA in DNA amp in RNA someRNA NHL 0 Purlnes doublering aromatic 1 1 H i N h N r N compound N1 vC7 NK 7 N 7 It III gtCII I in 7111 I H 7211 HC IIt N HN I 1 H H 3 H Purine Adenine Guanine in DNA 8c RNA in DNA 8c RNA ms arms rrrrrrrrr m DNA Structure double helix structure Nucleotide bases made up of a nucleic acid ribose sugar and a phosphate base refers to a ring structure not as in pH Nucleoside a base and a sugar NH2 covalently bound to Clj lct each other Nf BCH named for the parent l1 base C Ribonucleoside a base bound to a ribose sugar DNA utilizes deoxyribonucleosides Cytidine Deoxyguanosine A ribonucleoside A deoxyribonucleoside mane mums mmn DNA Structure double helix structure Nucleotide bases made up of a nucleic acid ribose sugar and a phosphate base refers to a ring structure not as in pH Nucleotide phosphate group phosphoric acid esteri ed to the 5 hydroxyl group of bosesugarofanucbogde nanmdfm1hepamntnudeo de N112 H l dAMP l 07 I 7071 H n lIl H lhnuilnmitlim39 5 uunuplI lllmw uelllAuv tll2 U l H n u l u n dCMP l II II Dunurvtidinc 3IIHUIIIIPIIHSIJIIJIL39 DNA Structure double helix structure Formation of sugarphosphate backbone l Individual nucleotides are connected 3K2 through linking the 3 OH ribose 005H IRA H g group with the phosphate group 7 2 quot quotquotquotquotquot39 autumn W on the 5 OH of adjacent ribose NTLNu 3il39rt393139l 2 539lxMW lialImtlimlu I 7039 IH2 0 lt 39Hg Guanine 7 tH2 Sugarphosphate backbone repeats down 3 0 x the length of chain Uzi mill 0 N 70 I Mtg Identity of the bases determines quot0 39 K DNA sequence zll05Hu Kb 7 Adu nc T TGCA WTtI minus ozone avcnxscnze Truman 1 DNA Structure N 2 double helix structure Wk 11 n N N Directionality of a single DNA strand 391 f0jquot1 2 I 0 II gt I 11 H 5 TGCA3 k i J 5 end start of gene 0 39 awm W a K iuIw 4nv lilmlt 3 end end of gene w H h N 33 0 lt 1391 mmlw1 0 70612 0 N XHU mm hum A 390 1 NH2 Ultimater 5 end of a gene Ntermlnus of protein w L V 3 end ofa gene Cterminus of protein 1 T quot A p gtH2 0 0 Cmm 7 W Mtg 0 H n l quot1Hu 39JV Adminc l J 91 EIZOUS Ercnkscnle Human li 20 A dunquot 16 Lnrgv gruuw in dupqu Small grow in rluplvx r l 2 Tlu hm Imml lmu V c2005 Biwu Cn39g Thurman upstilc poLu as annpzuallcl r 7 397 x 4 DNA Structure double helix structure M A Length ofonc mmpim mm Two complementary DNA strands in a double helix Early experiments showed that the amount of G C A T indicated that Base pairs on one strand are complementary to the base pairs on the other side Adenine Thymine purine pyrimidine Guanine cytosine purine pyrimidine Strands run in antiparallel opposite directions 5 G A T C 3 3 C T A G 5 DNA Structure double helix structure Outside diameter 20 nm 20 nm l3 2quot 5 jquotquotquotl Inside diameter 11 nm Length of one turn 10 base pairs mm 34 nm induplg x 22 nm ligummm Empty spaces in helix not filled by atoms Small gramme mmplvm mm in K upltx 34 nm I H Major large groove 22 nm 12 nm Tlu u liulmb imu 39 upstilC pohrity annpzu allol Minor small groove 12 nm places where proteins can bind bases of DNA Double Helix Structure c2005 BlankCu Thurman DNA Structure double helix structure Base pairs Adenin Thynine 1m hydrnge bum Ir Hs i I llllllllllllllllllllll I ll mi H N H N y H WHHMWW x V V Nll lluui lt f I 39 2 H I bond H A II II N H H in mm llil mm H H m l V 39 I N I h Hmmrmmii lt mi Y N i lt N H II 4amp mullulululll l HI I 17 in mm 5 N II II A o mas Emuksicnle mmson purine pyrimidine base pairing allows for smooth backbone with out bulges gives consistent double helix diameter of 2 nm Hbonds are perpendicular to the helix axis DNA Structure double helix structure BDNA form we have discussed predominant normal or goth fortnigyouue physiological form of DNA tire4amp1 Erma u y A A DNA base pair Hbonds at 20 angle 13 11 base pairs per helix turn 523w a v Q more compact than BDNA siif x forms under low hydration W t fwaw H d h I I DNA 5 h M no oun in p ysio ogica M 2 ZDNA forms in regions of DNA with alternating purinepyrimidine sequence CGCGCGCG is in physiological DNA longer and thinner than BDNA 12 bases per helix turn c 2005 BrooksCola Thomson DNA Structure double helix structure Both 8 and ADNA are Other forms of double helix righthanded helices 3933 H gt quot3 3k a ZDNA is a lefthand helix LE 2005 BrooksCale Thomson 2005 Evnaksscmemnmsan DNA Structure How does so much DNA t into a cell or nucleus DNA Supercoiling Supercoiling twisting of double helix in space about its axis Supernoil DNA Structure DNA Supercoiling Supercoiling twisting of double helix in space about its axis Prokaryotic DNA supercoiling prokaryotic DNA is found as circular twists in circular structure give extra twist to DNA positive supercoil right handed or clockwise twist negative supercoil lefthanded or counterclockwise twist naturallv occurrino form of circular DNA A W r it x V all negative Rtlaxcd positive supercoil supercoil its DNA Structure DNA Supercoiling Eukaryotic DNA supercoiling more complex than circular DNA of prokaryotes DNA is not circular DNA has an overall negative charge DNA complexes with positively charged proteins kxH called histones A0 arm miqu H36 0 i l gt y oiyzn 0 Thymim lt7 i 0 A Histories proteins associated with Eukaryotic DNA NH I T basic proteins with large amounts 01705542 0 39 N C of basic amino acids Lys amp Arg 0 i quot2 5 main types H1 H2A H28 H3 and H4 l 3 7 Oil our 0 ZDDSEiDNScul Timman DNA Structure Eukaryotic DNA Supercoiling Chromatin the complex of DNA and proteins that make up chromosomes resembles beads on a string in unpacked state FA zJ V is coiled into tight packing to form chromosome l V J j N I I Nucleosome DNA wrapped around a histone core fatquot histone core octamer of H2A2HZB2H32H42 H1 holds DNA around histone core 1 rm u l mule r quot IT um nu m of DNA DNA packing of nucleosomes makes up chromatin DNA Structure Eukaryotic DNA Supercoiling Nucleosome 150 base pairs of DNA wrapped around histone core 30 50 base pairs of DNA in spacer region Nucleosome Core nfeighl llislum molculics wrappul u lh two turns of DNA DNA Single hislom39 molecule holds 4 DNA In core chromatin formation QZDWBXDWCaleTmmn DNA Replication DNA replication takes place once each generation in each cell DN 4 l Wit with l W RNA and protein synthesis occur many times in one generation ofa cell Differences in details of DNA replication between eukaryotes and prokaryotes But basic mechanism is the same DNA Replication 3 possible modes of DNA replication 1 Semiconservative each strand is copied and resulting DNA has one new and one original strand 2 Conservative only new strand copies associate with each other and only original strands associate with each other 3 Dispersive resulting DNA mixture of new and original DNA Tiucw postulath methods or DNA Replication WWW lt1Um ym l mt m m WWWWWW Semi Conservative WWltWW Conservative WWltZ Dispersive W x l W Newly synthesized Strand Originalremplatestrand DNA Replication Meselson Stahl Experiment Semiconservative Replication Experiments Frank Stahlr Matthew Mesieison 1958 at Cal Tech 23 used 15N natural isotope 14N L A44 I 7 Fed 15N traced incorporation into DNA over generations i f i 4 Used bacteria E coli CSHL h39L Both American born scientists DNA Replication Semiconsenative Replication Experiments c0 c0 RED 15N InitialpenumDNA Start Wlth 15N labeled DNA 14N 1Ih rl39illl 5N Ga lt1 lt 0 Firtcpmm After first replication each DNA double helix should 2 l quotli be 50 50 15N 14N 59mmmsrndliuM39leicnlirm G 3 392 iquot quot W 2 C After second replication 50 of DNA double helices should be 50 50 Spuranir plimliun 15N 14N in IHL39KIIUHI with l N 2 mos Emucm Ivunsun DNA Replication DNA has origins of replication locations where DNA replication begins DNA replication is bidirectional Replication fork point at which new DNA strands are formed a P ukatyulic b Enkaryuuc ongim 511 2 i731 g 2 Early stage In rcpllrminn 21 g W mm M TL r5 W W Ialcr Stage in rcpliriiiion Replication on ks Writ wwwemawaw lt gt39Q ghmww 3 Daughter lupltx ox 7 U 71 Yahth a was Emukslcole mmmm DNA Replication DNA Polymerase enzyme that catalyzes the successive addition of each new nucleotide to the growing DNA chain 0 is a multisubunit enzyme 10 subunits H v 0 B lf H I39t 5 different DNA polymerases prokaryotes VV 4quot eukaryotes 0LBy68 Growingchaiu ii i all P7P70 POillli 0 Bast2 l l l l 7 Oi 7 I Nucleotide 2 I I 0 ll P o H2 0 Bust39 0 ll ll Nm plumphuilirxlm 7 hum l 2112 0 Base 1 l 1 i 0 l lt 3 Elongated chain o 2015 Emoksicule A Thomson DNA Replication Unwinding of DNA duplex Helicase enzyme that separates DNA duplex for replication Problem iftwo strands of DNA duplex are separated the DNA duplex ahead of separation would bunch up and stop replication Creates tenym Overcome by the enzyme Prokaryotes DNA gyrase enzyme that cuts DNA duplex relaxes DNA ahead ofduplex separation then rejoins duplex Eukaryotes Topoisomerase performs same function in eukaryotes DNA Replication Proofreading and Mutations DNA replication error mismatched base pairs G T or C A Errors occur one in every 109 one billion to 1010 ten billion base pairs DNA polymerase has proofreading capability Can fix mismatches as it makes new DNA Tclnplatc Mismatchcd Exomlclease hydrnlwis si e polymerase I mans Emuksi coln rl39humson DNA polymerase Prokaryotic DNA Replication newly synthesized strand 5 mung wand Imuplmc template DNA gy rase om Chamki frngm ml e was Emcmcnim Thuquotsun Eukaryotic DNA Replication template newly synthesized strand t P iS merase i I p 39739 1 Iquot 3 f ll i I 39 3 Igg1ng auditmph valvsmihcsiLLl 1quot I I Rxwm mm quotquot W quotWWWquot repllcation fork lLI IIVIIIUX M39 L D Pulmlvx39nsv a l G 1 Rapid grow 11 and metabolic DNA Replication When does DNA replication take place Prior to mitosis when cells must divide A new set of DNA is needed for new cells DNA replication is complex process in which errors can take place DNA replication and growth System has built in correction systems ex proof reading of DNA polymerase 39 2 Growth and preparation for cell