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1
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• ???????? ????????,
• ??????? ?????? ?? ????. ???????
• ????????? ????????, ?? ??. ??. ????????
• ???. ??. ?????? 5, 1164 ?????

2
?????? ?? ?2 ? ??2

• ???? ???????????? ??????? (????????? ??????
  ?????-????????????) ?? ??????? ???????? ?? ??????
  ??????? ??? ?????? ??????. ???? ????????? ???????
  ????? 280 ??? ???????? ????????????? ????????
  Hb. ??? ??????? ?2,? ? ??????? ?????? ??2.
• ? ????????? ?? ??????????? ??????? ?????????
  Mb.

3
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Mb (a monomer containing 8 a -helices, A-H) and
Hb (a heterotetramer with two a -and two
ß-subunits, each which also contains 8 a
-helices) are both oxygen binding proteins.
a 141 ?.?. ß -146 ?.?.
http//themedicalbiochemistrypage.org/hemoglobin-m
yoglobin.html
4
Hb

• Hemoglobin
• 1st. protein whose molecular weight was
  determined
• 1st protein to be assigned a specific function -
  dioxygen transport
• has a prosthetic group (non-amino acid) heme
  group (protoporphyrin IX with a ferrous ion)
  covalently attached to the protein.  The heme
  group binds dioxygen. 
• 1st protein in which a point mutation (single
  base pair charge) causes a single amino acid
  change in the protein, marking the start of
  molecular medicine (0??? 574 ?.?. 2 ???????? ?
  ß ???????? ???-???)
• 1st protein with high resolution x-ray structure
• theory for dioxygen binding explain control of
  enzyme activity
• the binding of dioxygen is regulated by binding
  of H, CO2, and bisphosphoglcyerate which bind to
  sites (allosteric) distant from oxygen binding
  site.
• crystals of deoxy-Hb shatter on binding dioxygen,
  indicating significant conformational changes on
  binding.

5
???????? ?? ???????????
6
????????? ?? ???????????
???????????? ? ?????? ? ??????????? ????????? ?
????????? ???? ????? 66000-68000 Da. ????????????
?????????? ?? ???? ? ??????? ??????. ???????? ?
????????, ?.?. ????? ???????? ??????? 2 ???? ? 2
????-???????????? ??????, ??????????? ?? ??
?????????? ?? ????????? (???? ??????????????
?????? ??????? 141 ?????????????? ????????, ?
???? ?????????????? ?????? - 146 ??????????????
????????). ?????????? ?? ????????? ?? ???????????
?? ???????? ???????? ? ???????? ???????. ??
???????? ????????? ????? ???? ?????? ?? ??????,
???? ????? ?? ???????????? ??????? ??????????
????, ? ????? ???? ?? ???????? ?? ???? ????????
???. ?????? ?? ?? ????????, ?? ??????????? ? ????
????? ???? ????? ?????????????? ??????, ???????
????? ?????? ? ?????????????? ?????? ??
????????????? ??????. ???? ?? ????????????????
?????? ?????? ???????? ? ?? ?????? ? ???????? ???
? ????? ??????????, ???? ?????????? ???? (??),
?????????? ??????? (??2), ??????? ? ?.?
7
????????? ?? ????
8
(No Transcript)
9
In addition, crucial H-bonds between Tyr 140
(alpha chain) or 145 (on the beta chain) and the
carbonyl O of Val 93 (alpha chain) or 98 (beta
chain) are broken. Crystal structures of oxy and
deoxy Hb show that the major conformational shift
occurs at the interface between the a and b
subunits. When the heme Fe binds oxygen it is
pulled into the plan of the heme ring, a shift of
about 0.2 nm. This small shift leads to larger
conformational changes since the subunits are
packed so tightly that compensatory changes in
their arrangement must occur. The proximal His
(coordinated to the Fe) is pulled toward the
heme, which causes the F helix to shift, causing
a change in the FG corner (the sequence
separating the F and G helices) at the alpha-beta
interface as well as the C and G helices at the
interface, which all slide past each other to the
oxy-or R conformation.
10
Based on crystallographic structures, two main
conformational states appear to exists for Hb,
the deoxy (or T - taut) state, and the oxy(HbO2)
(or R -relaxed) state. The major shift in
conformation occurs at the alpha-beta interface,
where contacts with helices C and G and the FG
corner are shifted on oxygenation. The deoxy or
T form is stablized by 8 salt bridges which are
broken in the transition to the oxy or R state.
11
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12
?????? ?? ??2
CO2 Hb-NH2 ltgt H Hb-NH-COO