@text "QUATERNARY STRUCTURE -- ASSOCIATION OF INEQUIVALENT SUBUNITS AND EVOLUTIONARY CONSERVATION (HEMOGLOBIN)" Hemoglobin is an oxygen binding and transport protein found in a wide range of species, including humans. It consists of four chains (two inequivalent pairs) which associate with one another to form the active species. Each pair consists of two identical subunits (i.e., there are two A-type chains and two B-type chains; each type contains a 'globin fold'). Kinemage 1 allows you to compare two normal hemoglobin proteins from species at different points in the evolutionary spectrum (fish and human; from PDB files, 1PBX & 1HHO, respectively). This represents a classic example of 'evolutionary conservation', meaning that the 3-D structure and function of the protein has undergone minimal change over the course of evolution. This does not imply that the amino acid sequences are equivalent, or even close; simply that the conformations of the folded proteins are very similar. This is true for hemoglobins from a variety of other species, as well. One can also compare normal human hemoglobin to the abnormal human hemoglobin responsible for the serious disease known as 'sickle-cell anemia' (from PDB file, 1HBS). In the abnormal protein, one sidechain in the B-type subunit is different from the corresponding sidechain in the normal protein, caused by a genetic defect. This subtle change does not alter the overall 3-D structure of the protein, as can be seen by comparison of the two proteins. However, the specific amino acid change (mutation) is significant, as the negatively-charged, hydrophilic residue, glutamate, is replaced by the neutral, hydrophobic residue, valine. This results in the association of the abnormal protein with itself to form long protein strings that distort the shape of red blood cells (sickling). @kinemage 1 @caption Calpha superposition of human (seagreen) & fish (skyblue) hemoglobin tetramers, highlighting the similarity in structure. Repeatedly click on 'ANIMATE' to identify the two A-type & two B-type subunits. Turn off the fish protein, turn on 'sub 1' of the sickle-cell protein, select view2, & then repeatedly click on '2ANIMATE' to see the mutation responsible for this disease. Now select view3 & turn on 'sub 2' to see the interaction of two abnormal proteins. @thinline @zoom 1.90 @zslab 290 @center 0.634 -1.266 7.049 @matrix 1.000000 0.000000 0.000000 0.000000 1.000000 0.000000 0.000000 0.000000 1.000000 @2zoom 3.82 @2zslab 530 @2center -18.757 -23.041 6.372 @2matrix 0.889379 -0.085680 0.449070 -0.126804 0.897509 0.422373 -0.439233 -0.432594 0.787360 @3zoom 1.26 @3zslab 290 @3center -18.757 -23.041 6.372 @3matrix 1.000000 0.000000 0.000000 0.000000 1.000000 0.000000 0.000000 0.000000 1.000000 @group {HEMOGLOBN} @subgroup {Human-NRM} dominant @vectorlist {sub a1} color= seagreen {ca val a 1}P 6.87 17.784 4.702 {ca leu a 2}10.599 17.914 4.153 {ca ser a 3}12.286 19.774 7.034 {ca pro a 4}15.285 22.042 6.167 {ca ala a 5}17.533 19.415 7.651 {ca asp a 6}15.949 16.873 5.231 {ca lys a 7}16.748 19.222 2.352 {ca thr a 8}20.352 19.578 3.477 {ca asn a 9}20.656 15.777 3.689 {ca val a 10}19.211 15.132 0.217 {ca lys a 11}21.428 17.873 -1.33 {ca ala a 12}24.453 16.454 0.234 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136}8.23 -14.926 3.117 {ca val b 137}9.272 -14.226 6.696 {ca ala b 138}6.775 -11.355 7.002 {ca asn b 139}4.033 -13.558 5.601 {ca ala b 140}4.934 -16.379 7.962 {ca leu b 141}4.866 -14.075 10.953 {ca ala b 142}1.51 -12.675 9.894 {ca his b 143}-0.087 -16.074 9.182 {ca lys b 144}-1.697 -16.763 12.539 {ca tyr b 145}-3.162 -13.227 12.992 {ca his b 146}-6.965 -13.219 13.7 @vectorlist {sub a2} color=seagreen {ca val c 1}P -7.257 17.813 -4.805 {ca leu c 2}-10.931 18.37 -4.346 {ca ser c 3}-12.686 20.107 -7.229 {ca pro c 4}-15.723 22.283 -6.502 {ca ala c 5}-17.816 19.436 -7.791 {ca asp c 6}-16.13 17.033 -5.394 {ca lys c 7}-16.877 19.425 -2.517 {ca thr c 8}-20.471 19.72 -3.543 {ca asn c 9}-20.689 15.881 -3.764 {ca val c 10}-19.207 15.406 -0.368 {ca lys c 11}-21.405 18.065 1.37 {ca ala c 12}-24.406 16.564 -0.228 {ca ala c 13}-23.664 12.983 0.745 {ca trp c 14}-22.515 13.791 4.276 {ca gly c 15}-25.57 16.035 4.594 {ca lys c 16}-27.917 13.063 3.99 {ca val c 17}-25.872 11.209 6.637 {ca gly c 18}-26.8 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2.743 -11.827 {ca pro e 95}1.015 4.294 -8.755 {ca val e 96}1.465 0.911 -6.563 {ca asn e 97}4.416 1.088 -9.039 {ca phe e 98}6.07 4.469 -8.191 {ca lys e 99}6.41 2.672 -4.817 {ca leu e 100}8.356 -0.058 -6.453 {ca leu e 101}11.044 1.742 -8.673 {ca ser e 102}11.748 4.371 -5.794 {ca his e 103}12.809 1.316 -3.475 {ca cys e 104}15.048 -0.151 -6.226 {ca leu e 105}16.714 3.241 -6.64 {ca leu e 106}17.464 3.578 -2.909 {ca val e 107}19.008 -0.125 -2.786 {ca thr e 108}20.597 0.947 -5.843 {ca leu e 109}21.857 4.21 -4.474 {ca ala e 110}22.62 2.16 -1.286 {ca ala e 111}25.004 -0.177 -3.098 {ca his e 112}27.064 2.522 -4.845 {ca leu e 113}28.084 4.979 -2.316 {ca pro e 114}29.637 2.73 0.217 {ca ala e 115}28.888 5.43 2.928 {ca glu e 116}27.144 8.831 2.269 {ca phe e 117}23.969 6.723 2.875 {ca thr e 118}23.713 6.984 6.715 {ca pro e 119}20.813 6.212 8.693 {ca ala e 120}19.232 9.636 8.151 {ca val e 121}20.097 10.007 4.643 {ca his e 122}18.319 6.58 3.615 {ca ala e 123}15.424 8.525 5.216 {ca ser e 124}15.524 11.875 3.316 {ca leu e 125}16.401 9.912 0.135 {ca asp e 126}13.21 8.025 1.267 {ca lys e 127}10.749 11.073 1.231 {ca phe e 128}12.349 12.954 -1.665 {ca leu e 129}11.689 10.07 -3.767 {ca ala e 130}8.367 9.599 -2.116 {ca ser e 131}7.97 13.185 -2.692 {ca val e 132}8.763 12.743 -6.363 {ca ser e 133}6.192 9.897 -6.861 {ca thr e 134}3.493 12.172 -5.471 {ca val e 135}3.967 15.108 -8.028 {ca leu e 136}4.113 12.504 -10.641 {ca thr e 137}0.982 11.081 -9.323 {ca ser e 138}-0.894 14.234 -8.991 {ca lys e 139}-3.095 14.861 -12.129 {ca tyr e 140}-4.584 11.504 -12.358 {ca arg e 141}-8.229 11.9 -11.305 {ca val f 1}P 7.273 -16.69 -3.542 {ca his f 2}9.114 -19.864 -4.952 {ca leu f 3}12.942 -20.497 -4.639 {ca thr f 4}15.002 -21.833 -7.573 {ca pro f 5}18.051 -23.887 -7.046 {ca val f 6}20.21 -20.979 -8.101 {ca glu f 7}18.486 -18.321 -6.178 {ca lys f 8}18.284 -20.876 -3.538 {ca ser f 9}22.019 -21.333 -4.492 {ca ala f 10}22.253 -17.65 -4.151 {ca val f 11}20.549 -16.337 -0.876 {ca thr f 12}22.389 -19.182 0.698 {ca ala f 13}25.795 -17.879 -0.105 {ca leu f 14}25.409 -14.111 0.556 {ca trp f 15}23.706 -15.235 3.695 {ca gly f 16}26.887 -17.258 3.82 {ca lys f 17}28.914 -14.118 4.808 {ca val f 18}26.92 -12.077 7.312 {ca asn f 19}27.135 -11.379 11.057 {ca val f 20}23.205 -11.009 11.984 {ca asp f 21}24.278 -9.363 15.117 {ca glu f 22}25.967 -6.758 13.332 {ca val f 23}23.46 -6.999 10.484 {ca gly f 24}19.993 -6.463 12.448 {ca gly f 25}20.811 -3.758 14.958 {ca glu f 26}20.96 -1.932 11.578 {ca ala f 27}17.69 -2.879 9.93 {ca leu f 28}15.587 -2.331 13.04 {ca gly f 29}17.528 0.947 13.983 {ca arg f 30}17.019 1.824 10.475 {ca leu f 31}13.224 0.992 10.088 {ca leu f 32}13.208 2.559 13.404 {ca val f 33}14.511 5.916 11.83 {ca val f 34}13.12 6.006 8.097 {ca tyr f 35}9.717 5.191 9.09 {ca pro f 36}9.479 6.365 12.787 {ca trp f 37}5.837 5.043 13.485 {ca thr f 38}7.751 1.878 14.013 {ca gln f 39}8.963 3.197 17.432 {ca arg f 40}5.196 2.614 18.499 {ca phe f 41}6.2 -0.702 20.078 {ca phe f 42}9.482 0.51 21.659 {ca glu f 43}9.532 3.154 24.315 {ca ser f 44}10.526 0.666 26.771 {ca phe f 45}13.898 1.087 24.934 {ca gly f 46}15.269 4.371 26.272 {ca asp f 47}16.331 7.315 23.963 {ca leu f 48}14.971 6.804 20.308 {ca ser f 49}14.777 10.543 19.758 {ca thr f 50}17.406 10.815 17.135 {ca pro f 51}19.075 8.316 14.838 {ca asp f 52}22.44 8.259 16.636 {ca ala f 53}20.289 7.931 19.706 {ca val f 54}18.683 5.231 17.514 {ca met f 55}21.836 3.201 16.331 {ca gly f 56}23.591 3.116 19.724 {ca asn f 57}20.693 2.033 21.911 {ca pro f 58}21.502 -1.485 23.068 {ca lys f 59}17.84 -2.706 23.77 {ca val f 60}17.851 -2.072 19.818 {ca lys f 61}20.86 -4.046 18.63 {ca ala f 62}19.628 -6.58 21.064 {ca his f 63}16.126 -7.482 19.966 {ca gly f 64}17.531 -6.283 16.699 {ca lys f 65}19.75 -9.472 16.673 {ca lys f 66}16.866 -11.475 18.278 {ca val f 67}14.722 -10.589 15.306 {ca leu f 68}17.368 -11.64 12.8 {ca gly f 69}19.009 -14.982 14.058 {ca ala f 70}15.335 -15.761 14.928 {ca phe f 71}15.277 -15.331 11.162 {ca ser f 72}18.359 -17.518 9.972 {ca asp f 73}15.691 -20.132 10.02 {ca gly f 74}13.555 -18.638 7.148 {ca leu f 75}16.731 -19.55 5.333 {ca ala f 76}17.122 -22.79 6.934 {ca his f 77}13.582 -23.978 6.186 {ca leu f 78}12.482 -22.119 2.788 {ca asp f 79}10.853 -25.325 2.759 {ca asn f 80}8.265 -24.155 5.179 {ca leu f 81}8.363 -20.537 6.857 {ca lys f 82}4.828 -21.398 7.504 {ca gly f 83}5.039 -24.05 10.257 {ca thr f 84}8.544 -22.834 11.034 {ca phe f 85}6.73 -19.483 11.891 {ca ala f 86}3.124 -20.187 13.073 {ca thr f 87}4.269 -19.749 16.62 {ca leu f 88}5.77 -16.342 16.294 {ca ser f 89}2.762 -14.986 14.161 {ca glu f 90}0.099 -16.544 16.466 {ca leu f 91}2.485 -14.748 18.824 {ca his f 92}2.753 -11.365 17.054 {ca cys f 93}-0.93 -11.051 16.488 {ca asp f 94}-2.767 -11.795 19.681 {ca lys f 95}0.054 -10.677 22.11 {ca leu f 96}2.396 -7.974 20.488 {ca his f 97}-0.713 -7.086 18.366 {ca val f 98}1.802 -5.923 15.669 {ca asp f 99}0.866 -4.975 12.069 {ca pro f 100}2.186 -7.277 9.421 {ca glu f 101}2.679 -4.252 7.217 {ca asn f 102}5.494 -3.913 9.477 {ca phe f 103}7.417 -7.238 8.244 {ca arg f 104}7.038 -5.872 4.827 {ca leu f 105}8.426 -2.716 6.28 {ca leu f 106}11.56 -4.592 8.038 {ca gly f 107}11.475 -6.738 4.98 {ca asn f 108}12.583 -4.007 2.684 {ca val f 109}15.292 -1.747 4.774 {ca leu f 110}16.664 -5.176 5.299 {ca val f 111}17.219 -5.553 1.593 {ca cys f 112}18.602 -2.067 1.657 {ca val f 113}21.175 -2.859 4.452 {ca leu f 114}22.276 -6.066 2.619 {ca ala f 115}23.098 -3.953 -0.191 {ca his f 116}24.695 -1.249 2.067 {ca his f 117}27.177 -4.17 2.617 {ca phe f 118}28.002 -6.183 -0.508 {ca gly f 119}27.933 -3.243 -2.987 {ca lys f 120}28.241 -4.889 -6.364 {ca glu f 121}28.623 -8.353 -4.665 {ca phe f 122}24.692 -8.082 -4.328 {ca thr f 123}23.326 -7.923 -7.937 {ca pro f 124}19.539 -7.842 -9.163 {ca pro f 125}19.275 -11.548 -9.491 {ca val f 126}20.514 -11.713 -5.881 {ca gln f 127}17.845 -9.111 -4.423 {ca ala f 128}15.048 -10.594 -6.331 {ca ala f 129}15.874 -14.113 -4.824 {ca tyr f 130}16.122 -11.932 -1.781 {ca gln f 131}12.715 -10.067 -2.422 {ca lys f 132}11.69 -13.573 -2.866 {ca val f 133}12.262 -14.613 0.88 {ca val f 134}11.91 -11.304 2.385 {ca ala f 135}8.201 -11.564 1.205 {ca gly f 136}7.351 -15.282 2.116 {ca val f 137}8.955 -14.777 5.502 {ca ala f 138}6.861 -11.579 5.578 {ca asn f 139}3.839 -13.554 4.417 {ca ala f 140}4.788 -16.391 6.903 {ca leu f 141}4.958 -13.991 9.753 {ca ala f 142}1.181 -12.899 8.921 {ca his f 143}-0.251 -16.242 8.01 {ca lys f 144}-2.154 -16.463 11.417 {ca tyr f 145}-3.77 -12.945 11.714 {ca his f 146}-7.374 -13.384 13.034 {ca val g 1}P -6.977 18.406 -5.075 {ca leu g 2}-10.794 18.217 -5.64 {ca ser g 3}-12.385 20.302 -8.646 {ca pro g 4}-15.271 22.416 -7.719 {ca ala g 5}-17.243 19.778 -9.622 {ca asp g 6}-15.773 17.421 -6.772 {ca lys g 7}-16.546 19.955 -3.99 {ca thr g 8}-20.135 19.824 -4.925 {ca asn g 9}-20.91 15.942 -5.067 {ca val g 10}-18.955 15.383 -1.957 {ca lys g 11}-21.195 17.885 0.105 {ca ala g 12}-24.66 16.499 -1.344 {ca ala g 13}-24.241 12.824 -0.621 {ca trp g 14}-22.447 13.858 2.569 {ca gly g 15}-25.246 16.049 2.051 {ca lys g 16}-27.749 13.238 2.985 {ca val g 17}-25.996 11.25 5.767 {ca gly g 18}-26.259 14.605 7.624 {ca ala g 19}-27.769 12.673 10.442 {ca his g 20}-26.856 8.845 10.377 {ca ala g 21}-23.104 10. 10.15 {ca gly g 22}-23.082 9.047 13.556 {ca glu g 23}-24.144 5.576 11.968 {ca tyr g 24}-22.125 4.788 8.667 {ca gly g 25}-19.316 5.942 10.869 {ca ala g 26}-19.615 2.905 13.061 {ca glu g 27}-20.618 0.083 10.347 {ca ala g 28}-17.676 1.355 8.36 {ca leu g 29}-15.233 0.29 11.062 {ca glu g 30}-17.444 -2.601 11.918 {ca arg g 31}-16.924 -3.706 8.292 {ca met g 32}-13.208 -2.751 8.717 {ca phe g 33}-12.466 -5.323 11.245 {ca leu g 34}-14.266 -8.295 9.624 {ca ser g 35}-12.728 -7.996 6.05 {ca phe g 36}-9.375 -6.589 6.971 {ca pro g 37}-8.399 -8.248 10.169 {ca thr g 38}-4.85 -6.518 10.709 {ca thr g 39}-6.605 -3.208 11.704 {ca lys g 40}-7.54 -5.298 14.744 {ca thr g 41}-4.11 -4.739 16.353 {ca tyr g 42}-4.695 -1.069 16.738 {ca phe g 43}-7.553 -2.14 19.297 {ca pro g 44}-6.577 -4.68 22.19 {ca his g 45}-8.111 -2.014 24.236 {ca phe g 46}-11.263 -2.123 22.36 {ca asp g 47}-14.181 -4.35 22.712 {ca leu g 48}-14.872 -5.342 18.998 {ca ser g 49}-18.002 -7.439 19.582 {ca his g 50}-20.597 -6.089 17.259 {ca gly g 51}-22.738 -4.92 19.944 {ca ser g 52}-19.807 -3.167 21.301 {ca ala g 53}-20.57 -0.083 23.151 {ca gln g 54}-16.935 1.312 22.078 {ca val g 55}-16.578 0.624 18.385 {ca lys g 56}-19.913 2.382 18.705 {ca gly g 57}-18.162 5.311 20.209 {ca his g 58}-15.091 5.642 17.655 {ca gly g 59}-17.697 6.168 14.787 {ca lys g 60}-19.346 9.706 15.138 {ca lys g 61}-15.923 10.611 16.611 {ca val g 62}-15.162 9.045 13.254 {ca ala g 63}-17.866 10.768 11.072 {ca asp g 64}-17.755 13.947 13.159 {ca ala g 65}-14.261 13.44 12.17 {ca leu g 66}-15.24 13.624 8.448 {ca thr g 67}-18.067 16.329 8.329 {ca asn g 68}-15.893 18.808 10.006 {ca ala g 69}-14. 17.747 6.782 {ca val g 70}-16.518 18.581 3.872 {ca ala g 71}-17.35 21.48 6.125 {ca his g 72}-13.933 22.59 5.068 {ca val g 73}-12.832 20.895 1.916 {ca asp g 74}-10.817 24.143 1.039 {ca asp g 75}-7.903 23.261 3.099 {ca met g 76}-8.959 20.025 4.669 {ca pro g 77}-5.719 20.357 6.438 {ca asn g 78}-7.146 22.905 8.88 {ca ala g 79}-9.438 20.471 10.906 {ca leu g 80}-7.672 17.196 10.059 {ca ser g 81}-4.551 19.333 11.073 {ca ala g 82}-5.926 18.745 14.456 {ca leu g 83}-6.042 14.642 14.358 {ca ser g 84}-3.101 14.739 12.043 {ca asp g 85}-0.686 15.659 15.057 {ca leu g 86}-2.799 12.821 16.858 {ca his g 87}-2.612 9.992 14.431 {ca ala g 88}1.061 11.169 13.566 {ca his g 89}2.517 11.119 17.212 {ca lys g 90}-0.24 9.571 19.44 {ca leu g 91}-1.967 7.016 17.351 {ca arg g 92}0.956 6.127 15.018 {ca val g 93}-0.958 3.965 12.396 {ca asp g 94}0.693 3. 8.92 {ca pro g 95}-1.121 4.855 6.17 {ca val g 96}-1.476 1.355 4.735 {ca asn g 97}-4.834 1.147 6.468 {ca phe g 98}-5.899 4.686 5.89 {ca lys g 99}-6.911 3.141 2.574 {ca leu g 100}-9.123 0.454 3.902 {ca leu g 101}-11.745 2.069 6.092 {ca ser g 102}-11.83 4.721 3.428 {ca his g 103}-12.804 1.456 1.493 {ca cys g 104}-15.269 0.245 3.984 {ca leu g 105}-16.733 3.778 3.997 {ca leu g 106}-17.501 4.112 0.314 {ca val g 107}-19.121 0.753 0.782 {ca thr g 108}-21.14 1.511 3.931 {ca leu g 109}-22.224 4.428 2.063 {ca ala g 110}-22.794 2.57 -1.131 {ca ala g 111}-25.617 0.584 0.556 {ca his g 112}-27.205 3.581 1.978 {ca leu g 113}-27.19 5.868 -1.019 {ca pro g 114}-28.455 3.772 -3.955 {ca ala g 115}-28.858 6.88 -6.02 {ca glu g 116}-26.784 9.526 -4.47 {ca phe g 117}-24.14 7.243 -5.667 {ca thr g 118}-23.666 8.175 -9.437 {ca pro g 119}-20.831 6.263 -11.227 {ca ala g 120}-19.827 10.029 -11.081 {ca val g 121}-20.093 10.72 -7.219 {ca his g 122}-18.611 7.537 -6.496 {ca ala g 123}-15.424 8.894 -8.192 {ca ser g 124}-16.239 12.041 -6.093 {ca leu g 125}-16.258 10.107 -2.881 {ca asp g 126}-13.604 8.06 -4.166 {ca lys g 127}-11.255 11.163 -4.432 {ca phe g 128}-12.644 12.813 -1.391 {ca leu g 129}-11.069 10.345 1.043 {ca ala g 130}-7.537 9.836 -0.155 {ca ser g 131}-7.405 13.593 0.152 {ca val g 132}-8.778 13.066 3.754 {ca ser g 133}-6.318 10.263 4.142 {ca thr g 134}-3.518 12.45 2.537 {ca val g 135}-3.83 15.076 5.419 {ca leu g 136}-3.721 12.708 8.442 {ca thr g 137}-0.56 10.946 7.105 {ca ser g 138}1.241 14.206 6.508 {ca lys g 139}3.499 14.609 9.657 {ca tyr g 140}4.531 11.183 9.818 {ca arg g 141}8.284 11.899 8.216 {ca gly g 142}P 0.906 11.659 -7.288 {ca lys g 143}-0.336 14.675 -5.251 {ca gln g 144}-3.017 15.997 -7.635 {ca tyr g 145}-4.753 12.646 -8.272 {ca his g 146}-6.753 11.408 -5.308 {ca val h 1}P -4.996 -18.069 1.273 {ca val h 1}-4.996 -18.069 1.273 {ca his h 2}-7.537 -18.069 4.158 {ca leu h 3}-10.627 -19.703 2.916 {ca thr h 4}-13.799 -20.05 4.773 {ca pro h 5}-16.138 -23.166 4.226 {ca val h 6}-19.317 -21.375 5.3 {ca glu h 7}-17.728 -18.089 4.154 {ca lys h 8}-18.277 -19.679 0.781 {ca ser h 9}-22.263 -20.289 0.98 {ca ala h 10}-21.978 -16.501 1.307 {ca val h 11}-20.427 -15.864 -2.131 {ca thr h 12}-22.017 -18.803 -3.26 {ca ala h 13}-25.46 -17.904 -2.286 {ca leu h 14}-26.048 -14.118 -2.982 {ca trp h 15}-24.504 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