Protein Structures: Primary, Secondary, Tertiary, and Quaternary, Slides of Biochemistry

Download Protein Structures: Primary, Secondary, Tertiary, and Quaternary and more Slides Biochemistry in PDF only on Docsity! Amino Acids and Proteins Part Il e759 di Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 2 •  Many  rela)vely  small  pep)des  are  biochemically  ac)ve:   –  Hormones   –  Neurotransmi9ers   –  An)oxidants   •  Small  Pep)de  Hormones:   –  Best-­‐known  pep)de  hormones:  oxytocin  and  vasopressin     –  Produced  by  the  pituitary  gland   –  nonapep)de  (nine  amino  acid  residues)  with  six  of  the  residues  held  in  the   form  of  a  loop  by  a  disulfide  bond  formed  between  two  cysteine  residues   Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 5 ACTH – Adrenocorticotropic Hormone Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 6 Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 7 •  Pep)des  with  An)bio)c  Ac)vity:         Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 10 •  Pep)des  with  An)bio)c  Ac)vity:      Tyrocidines   –  Mixture   of   cyclic   decapep)des   produced   by   the   bacteria   Bacillus  brevis  found  in  soil   –  It  can  be  composed  of  4  different  amino  acid  sequences,  giving   tyrocidine  A–D.     –  Major  cons)tuent  of  tyrothricin  which  also  contains  gramicidin   –  First   commercially   available   an)bio)c,   but   has  been   found   to   be  toxic  toward  human  blood  and  reproduc)ve  cells.     –  It   has   a   unique   mode   of   ac)on   in   which   it   disrupts   the   cell   membrane   func)on,   making   it   a   favorable   target   for   engineering  deriva)ves.[   –  It   appears   to   perturb   the   lipid   bilayer   of   a   microbe's   inner   membrane  by  permea)ng  the  lipid  phase  of  the  membrane.     Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 11 Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 12 Small  Pep)de  Neurotransmi9ers   •  Enkephalins  are  pentapep)de  neurotransmi9ers   produced  by  the  brain  and  bind  receptor  within  the   brain       •  Help  reduce  pain   •  Best-­‐known  enkephalins:   –  Met-­‐enkephalin:  Tyr–Gly–Gly–Phe–Met   –  Leu-­‐enkephalin:  Tyr–Gly–Gly–Phe–Leu   Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 15 Section 20.7 Biochemically Important Small Peptides Return to TOC Copyright © Cengage Learning. All rights reserved 16 Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 17 •  General  defini)on:  A  protein  is  a  naturally-­‐occurring,  unbranched  polymer  in   which  the  monomer  units  are  amino  acids.   •  Specific  defini)on:  A  protein  is  a  pep)de  in  which  at  least  40  amino  acid  residues   are  present:   –  The  terms  polypep)de  and  protein  are  o[en  used  interchangeably  used  to   describe  a  protein   –  Several  proteins  with  >10,000  amino  acid  residues  are  known   –  Common  proteins  contain  400–500  amino  acid  residues   –  Small  proteins  contain  40–100  amino  acid  residues   •  More  than  one  pep)de  chain  may  be  present  in  a  protein:   –  Monomeric  :  A  monomeric  protein  contains  one  pep)de  chain     –  Mul)meric:  A  mul)meric  protein  contains  more  than  one  pep)de  chain   Section 20.8 General Structural Characteristics of Proteins Return to TOC 1o – AA seq; all covalent bonds between AA’s Section 20.8 General Structural Characteristics of Proteins Return to TOC — Defined as the sequence (order) of amino acid residues in a protein —  Leu-Gly-Thr-Val is different in 1° structure from Val-Leu-Gly-Thr — The 1° structure strongly influence the 3-D arrangement of proteins — Determines the 3-D structure of proteins which in turn, determines its properties Primary structure   Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC • 2o = repeating interactions between amino acid residues that are close together in the linear sequence of the protein Section 20.8 General Structural Characteristics of Proteins Return to TOC Secondary  structure   •  Arrangement in space of the atoms in the peptide backbone •  Repetitive interactions resulting from H-bonding between the amide and the carbonyl groups of the peptide backbone Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 27 •  Arrangement  of  atoms  of  backbone  in  space.   •  The  two  most  common  types  :  alpha-­‐helix  (a-­‐helix)  and  the  beta-­‐ pleated  sheet  (b-­‐pleated  sheet).   •  The  pep)de  linkages  are  essen)ally  planar  thus  allows  only  two   possible  arrangements  for  the  pep)de  backbone  for  the  following   reasons:   –  For  two  amino  acids  linked  through  a  pep)de  bond  six  atoms  lie   in  the  same  plane   –  The  planar  pep)de  linkage  structure  has  considerable  rigidity,   therefore  rota)on  of  groups  about  the  C–N  bond  is  hindered     –  Cis–trans  isomerism  is  possible  about  C–N  bond.   –  The  trans  isomer  is  the  preferred  orienta)on   Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 30 Alpha-­‐helix  (α-­‐helix)   •  A  single  protein  chain  adopts  a  shape  that  resembles  a  coiled  spring/  rod   like  (helix):   –  H-­‐bonding  between  same  amino  acid  chains  –intra  molecular   –  Coiled  helical  spring   –  R-­‐group  outside  of  the  helix  -­‐-­‐  not  enough  room  for  them  to  stay   inside   Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC α-­‐  helix  Proper)es   •  Structure repeats itself every 5.4 Å along helix axis (pitch of 5.4 Å) •  3.6 aa/turn, thus 5.4/3.6 = 1.5 Å rise per aa residue •  Every C=O and N-H group H-bonded to peptide bond 4 residues away [ie O (= i) to N(= i+4)]. e. g., ….MAMELKMLLKAM… : donor for A is 1st K, which is the hydrogen acceptor of the 2nd K Section 20.8 General Structural Characteristics of Proteins Return to TOC Helix  Disrup)on   2. Strong electrostatic attraction repulsion – due to proximity of several charged groups of the charged side chains : +-charged R, K & H; - charged E & D 3. Crowding (steric repulsion) – caused by proximity of several bulky side chains Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 36 Beta-­‐Pleated  Sheets   •  Completely  extended  amino  acid  chains   •  H-­‐bonding  between  two  different  chains  –  inter  and/or   intramolecular   •  Side  chains  below  or  above  the  axis   Section 20.8 General Structural Characteristics of Proteins Return to TOC β-­‐sheets   •  The  polypep)de  chain  is  nearly  fully  extended   •  H-­‐bonds  can  be  intrachain  (between  different  parts   of  a  single  chain)  or  interchain  (between  different   chains)   •  β-­‐sheet  is  constructed  by  combining  two  or  more   regions  of  the  polypep)de   Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Bends  and  Loops   •  Bends (reverse turns) – Reverse direction of the main polypeptide chain – Connect regions of more regular secondary structure (α- helix and β-sheets) •  β-bends (hairpin turn)- connect antiparallel polypeptides •  Loop – extended bend – Continuous segment of polypeptide chain that contains no periodic 2° structure Section 20.8 General Structural Characteristics of Proteins Return to TOC β-­‐  bend   • allows peptide chain to reverse direction • Stabilized by H-bonding • proline and glycine prevalent Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC •  3o - Spatial relationships among all aa’s in polypeptide •  Complete 3-D arrangement of the entire polypeptide Section 20.8 General Structural Characteristics of Proteins Return to TOC Ter)ary  Structure   •  Describes the positions of all atoms in a protein including side chains – Result of combining several motifs of secondary structure into a compact arrangement •  All the information needed to fold into native 3D structure is contained by the 1º structure Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC • 4o – arrangement of multiple polypeptide chains called subunits • Homodimers • Heterotetramer Section 20.8 General Structural Characteristics of Proteins Return to TOC Quaternary  Structure   •  Defines the arrangement and position of each subunits in the intact protein molecule – Homotypic – association of identical or nearly identical subunits – Heterotypic - association of different subunits •  Ex: dimers, trimers, tetramers or oligomers •  Subunits interact with one another noncovalently via electrostatic attraction, H-bonds and hydrophobic interaction –  allosteric Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 56 •  Three  types  of  proteins:  fibrous,  globular,  and  membrane   •  Fibrous  proteins:  protein  molecules  with  elongated  shape:     –  Generally  insoluble  in  water   –  Single  type  of  secondary  structure   –  Tend  to  have  simple,  regular,  linear  structures     –  Tend  to  aggregate  together  to  form  macromolecular  structures,  e.g.,  hair,   nails,  etc   •  Globular  proteins:  protein  molecules  with  pep)de  chains  folded  into   spherical  or  globular  shapes:   –  Generally  water  soluble  –  hydrophobic  amino  acid  residues  in  the  protein   core   –  Func)on  as  enzymes  and  intracellular  signaling  molecules   •  Membrane  proteins:  associated  with  cell  membranes   –  Insoluble  in  water  –  hydrophobic  amino  acid  residues  on  the  surface   –  Help  in  transport  of  molecules  across  the  membrane   Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 57 Fibrous  Proteins:  Alpha-­‐Kera)n   •  Provide  protec)ve  coa)ng  for  organs   •  Major  protein  cons)tuent  of  hair,  feather,  nails,  horns   and  turtle  shells   •  Mainly  made  of  hydrophobic  amino  acid  residues   •  Hardness  of  kera)n  depends  upon  -­‐S-­‐S-­‐  bonds       •  more  –S-­‐S–  bonds  make  nail  and  bones  hard   Section 20.8 General Structural Characteristics of Proteins Return to TOC β-­‐Kera)n   •  Contain much more β-sheet structure •  Found mostly in birds and reptiles – feathers and scales Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 61 Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 62 Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 65 Fibrous  Proteins:  Collagen     •  Most  abundant  proteins  in  humans  (30%  of  total   body  protein)   •  Major  structural  material  in  tendons,  ligaments,   blood  vessels,  and  skin   •  Organic  component  of  bones  and  teeth   •  Predominant  structure  -­‐  triple  helix   •  Rich  in  proline  /  hydroxyproline  (up  to  20%)  –   important  to  maintain  structure   Section 20.8 General Structural Characteristics of Proteins Return to TOC Collagen •  Major protein of skin, bone and tendons •  Consists of repeating units of Pro-Gly-X or Hyp-Gly-X, Hyp – 4- hydroxyproline and X – any amino acid •  Consist of three extended helical chains wrapped into a triple helix (superhelix) •  Held by H-bonds involving hydroxyproline and hydroxylysine residues •  Very high strength with little ability to stretch desired for bones and tendons •  If proline is not hydroxylated to the usual extent, collagen will be less stable – cause scurvy Section 20.8 General Structural Characteristics of Proteins Return to TOC Triple helix Section 20.8 General Structural Characteristics of Proteins Return to TOC Myoglobin   Copyright © Cengage Learning. All rights reserved 70 Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 71 Globular  Proteins:  Hemoglobin   •  An  oxygen  carrier  molecule  in  blood   •  Transports  oxygen  from  lungs  to  )ssues   •  Tetramer  (four  pep)de  chains)  -­‐  each  subunit  has  a   heme  group   •  Can  transport  up  to  4  oxygen  molecules  at  )me                  Hb    +  4O2  =  Hb(O2)4   •  Iron  atom  in  heme  interacts  with  oxygen   Section 20.8 General Structural Characteristics of Proteins Return to TOC Hemoglobin •  Transport oxygen over large distances via the blood of aerobic organism •  Contains 4 polypeptide chains and four heme groups Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Heme Prosthetic Group •  The four heme groups serve as the sites for oxygen binding and so each hemoglobin molecule is able to bind, reversibly, 4 molecules of oxygen Section 20.8 General Structural Characteristics of Proteins Return to TOC Affinity of Oxygen Binding •  Cooperative binding – when one oxygen molecule is bound, it becomes easier for the next oxygen to bind •  Allosteric interaction - subtle conformational changes that is triggered by small changes at contact points between the subunits – Disruption of ionic linkages Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Hemoglobin Action •  In the alveoli of lungs – the pO2 is 15 kPa –  Hemoglobin is more than 95% saturated with oxygen •  In resting muscles - the pO2 is ~ 5 kPa –  Hemoglobin is about 75 % saturated •  In working muscles – the pO2 is 1-2 kPa –  Hemoglobin is 10% saturated Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Conformational Changes •  In the deoxy state, Fe 2+ in each heme is out of the heme plane by about 0.5 Å •  When O2 is bound, ferrous ion moves into the center of the heme – This movement pulls His F8 along with its polypeptide chain – Cause the rotation by about 15° of the two αβ units Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Section 20.8 General Structural Characteristics of Proteins Return to TOC Action of H+ •  Actively metabolizing tissues that require oxygen release H+ making hemoglobin lower its affinity for O2 •  In the muscle capillaries, H+ promotes the release of oxygen by favoring the deoxy form •  When blood recirculate to the lungs, the oxygenation has the effect of releasing H+ Section 20.8 General Structural Characteristics of Proteins Return to TOC Action of CO2 •  Large amounts of CO2 – produced during metabolism •  CO2 undergoes the bicarbonate reaction in physiological pH –  CO2 + H2O ↔ HCO3- + H+ •  HCO3- is transported to the lungs where it combines with the H+ released during oxygenation producing H2CO3 •  R-NH2 + CO2 ↔ R-NH-COO- + H+ Section 20.8 General Structural Characteristics of Proteins Return to TOC 2, 3 - bisphosphoglycerate Effect of 2,3 BPG •  2,3 Biphosphoglycerate is the most abundant organic phosphate in the RBC •  2,3-BPG is produced from 1,3 BPG (glycolytic pathway) •  It binds to deoxyHb and decreases O2 affinity to Hb and stabilizes the T conformation Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 95 Major  Categories  of  Proteins  Based  on  Func)on   •  Cataly)c  proteins:  Enzymes  are  best  known  for  their  cataly)c  role.   –  Almost  every  chemical  reac)on  in  the  body  is  driven  by  an  enzyme   •  Defense  proteins:  Immunoglobulins  or  an)bodies  are  central  to   func)oning  of  the  body’s  immune  system.   •  Transport  proteins:  Bind  small  biomolecules,  e.g.,  oxygen  and  other   ligands,  and  transport  them  to  other  loca)ons  in  the  body  and  release   them  on  demand.   •  Messenger  proteins:  transmit  signals  to  coordinate  biochemical  processes   between  different  cells,  )ssues,  and  organs.     –  Insulin  and  glucagon  -­‐  regulate  carbohydrate  metabolism   –  Human  growth  hormone  –  regulate  body  growth   Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 96 Major  Categories  of  Proteins  Based  on  Func)on   •  Contrac)le  proteins:  Necessary  for  all  forms  of  movement.   –  Muscles  contain  filament-­‐like  contrac)le  proteins  (ac)n  and  myosin).     –  Human  reproduc)on  depends  on  the  movement  of  sperm  –  possible   because  of  contrac)le  proteins.   •  Structural  proteins:  Confer  s)ffness  and  rigidity     –  Collagen  is  a  component  of  car)lage  a   –  Kera)n  gives  mechanical  strength  as  well  as  protec)ve  covering  to   hair,  fingernails,  feathers,  hooves,  etc.   •  Transmembrane  proteins:  Span  a  cell  membrane  and  help  control  the   movement  of  small  molecules  and  ions.   –  Have  channels  –  help  molecules  can  enter  and  exist  the  cell.   –  Transport  is  very  selec)ve  -­‐  allow  passage  of  one  type  of  molecule  or   ion.   Section 20.8 General Structural Characteristics of Proteins Return to TOC Copyright © Cengage Learning. All rights reserved 97 Major  Categories  of  Proteins  Based  on  Func)on   •  Storage  proteins:  Bind  (and  store)  small  molecules.   –  Ferri)n  -­‐  an  iron-­‐storage  protein  -­‐  saves  iron  for  use  in  the   biosynthesis  of  new  hemoglobin  molecules.     –  Myoglobin  -­‐  an  oxygen-­‐storage  protein  present  in  muscle   •  Regulatory  proteins:  O[en  found  “embedded”  in  the  exterior  surface  of   cell  membranes  -­‐  act  as  sites  for  receptor  molecules   –  O[en  the  molecules  that  bind  to  enzymes  (cataly)c  proteins),  thereby   turning  them  “on”  and  “off,”  and  thus  controlling  enzyma)c  ac)on.   •  Nutrient  proteins:  Par)cularly  important  in  the  early  stages  of  life  -­‐  from   embryo  to  infant.     –  Casein  (milk)  and  ovalalbumin  (egg  white)  are  nutrient  proteins     –  Milk  also  provide  immunological  protec)on  for  mammalian  young.