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N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia [email protected] Prebiological synthesis and evolution of macromolecules Sergey Varfolomeyev
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Page 1: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia

[email protected]

Prebiological synthesis and evolution of macromolecules

Sergey Varfolomeyev

Page 2: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Origin of Life = Origin of self Proliferating Macromolecules

Page 3: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Life phenomena from point of view of polymer chemistry

Polycondensation – the same reaction for all biopolymers

Three-functional monomers Immense decrease of number of

macromolecules comparing to the number of possible variants

Page 4: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Decrease of macromolecules number

Biological systems implemented the extreme low part of possible macromolecular structures

Human genome 3.104 genes

Possible variants of protein structures (20 amino acids, 100 monomers in chain)

20 100 ~ 10 130

Page 5: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Natural (biological) polymers – products of polycondensation of three-functional monomers

Amino acids - polyamides (proteins)

Nucleotides - polyesters (DNA, RNA)

N

NN

N

NH2

O

HO

HH

HH

PO

O-

HO

O-

H2N CH C

CH2

OH

O

CH2

C

OH

O

N

NH2

ON

O

OHO

HH

HH

PO

O-

HO

O-

Page 6: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

A

YX

B

X

A

YX

B

YX+

- Interaction of A and B

minimum two types (A, B)

- electrostatic

- hydrophobic

- hydrogen bonds

Y -H2O

Page 7: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

All biomacromolecules (products of polycondensation) are unstable in water

Page 8: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Is it possible to have polycondensation process in water?

Thermocycling

Page 9: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Thermocycle – natural global cycle

ΔT - 200 - +200 - 20 - + 150 0 - + 120

Polymerization at high temperatures 120 – 200 OC (statistical number of polymers with different structures

and size) Reduction of temperature, solubilization in water

condensate Macromolecular selection of monomers by polymer

matrix Temperature increasing, polymerization, monomers on

matrix (template), formation of partly complementary chain

Page 10: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Natural (biological) polymers – productsof polycondensation of three-functional monomers

Amino acids - polyamides (proteins)

Nucleotides - polyesters (DNA, RNA)

Page 11: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

"Кинетика как наука о законах и механизме развития различных процессов в природе находит в области биологии почти неограниченные перспективы для теоретических исследований и практического применения."

Н.М. Эмануэль, 1966

Page 12: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

Kinetic theory describing and explain the dramatic reduction of the number of polymer structures in systems.

S.D.Varfolomeyev,Kinetic models of the prebiological evolution of macromolecules.Thermocycle as motive force of the process,Mendeleev Communications,2007,17,7-9

Page 13: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

Page 14: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

dNi\dt =kiNiki=kfi-kdi

ki >0 автоселекцияki <0 деградация

Комплексообразование мономера с полимером,как правило,стабилизирует макромолекулу против термической деструкции и гидролитического расщепления

Page 15: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

Page 16: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

Page 17: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

1

2

3

- segregation

- evolution

- autocatalysis, convergence explosion

part of the "positive" molecules

Page 18: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Copolymerization of three-functional monomers

Thermocycle is a method to change absolutelyimprobable events (probability 10 -50) to absolutely certain ones

(probability 1).S.Varfolomeyev,Mendeleev Comm.2007,17,7-9

Page 19: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Adsorption of monomers over polymer Formation of a complex between

monomer and polymer tends to stabilize macromolecule against thermal destruction and hydrolysis

Synthesis of new polymer is selective

Page 20: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Synthesis

Page 21: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

BA A+H2O

BA

A

Hydrolysis

Page 22: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Selection of monomers on polymer and synthesis of partly complementary chain

Page 23: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Polymerization

Hydrolysis

Triads of two monomers

Synthesis on polymer

Page 24: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Reactions

Page 25: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Equations

Page 26: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Equations

Page 27: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Increased stability of certain triplets

AAA

BBB

BBB

Accumulation of AAA and BBB, no monomer competition

BBA

AAB

AAA

AAA

BBA

Depletion of AAB due to monomer competition with more stable BBA

Page 28: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Selection principles(competitive advantages)

Greater thermodynamical stability

Greater hydrolysis resistanceVelocity of catalytic processes:

The most stable and «quick» wins!

Page 29: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Experiments

Page 30: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Thermogravimetric analysis (TGA)

Kinetics of weight reduction (water elimination) during the L-asp polycondensation

time, s

wei

gh

t, %

Page 31: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Unique for Russia combined mass-spectrometer ICR + ionic trap Finnigan LTQ-FT

Линейная ионная ловушка

FTMS Data

Магнит7 T

Электронная пушка

ИК-лазер

F = q(E + v x B)

F F

v

Bv

ω = qB/m –циклотронная частота

F = q(E + v x B)

F F

v

Bv

ω = qB/m –циклотронная частота

FT_time_domane2_FFT_FT #1 RT: 65.39 AV: 1 NL: 2.13E5T: FTMS + p ESI Full ms [ 110.00-2000.00]

200 400 600 800 1000 1200 1400 1600 1800 2000

m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Re

lative

Ab

un

da

nce

648.85

432.90

338.34

679.811296.67

998.96

784.41508.26

619.36

908.75324.43 1859.03

716.80

216.45 1028.53 1358.601237.09 1632.901453.75

Page 32: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

World of polypeptidesneg-F8p_10e3_200-2000_FT #1 RT: 18.02 AV: 1 NL: 3.84E3T: FTMS - p ESI Full m s [ 200.00-2000.00]

300 400 500 600 700 800 900 1000 1100 1200 1300

m /z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Re

lativ

e A

bu

nd

an

ce

592.138z=0

477.112z=0

707.165z=1

822.192z=1

574.128z=2

513.861z=0

937.218z=1358.841

z=0689.154

z=2459.101z=2

804.182z=2 959.200

z=1919.207

z=0380.823

z=0729.147

z=0

844.174z=0

614.120z=0

1052.245z=1

1074.226z=0755.674

z=0866.156

z=0 981.181z=0306.879

z=0 1167.273z=0

1096.212z=0

1233.624z=0

MS/MS approach

Sequencing of products of polycondensation

Page 33: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

H2N CH C

(CH2)4

O

NH2

HN CH C

(CH2)4

OH

O

NH2

HN CH C

(CH2)4

N

O

NH2O

O

N

O

O

CCHNH2

(CH2)4

O

NH2 n

n = 7, 8

H2N CH C

(CH2)4

N

O

NH2O

O

NH

4O

O

HO

N

O

O

N

O

O

4

H2N CH C

(CH2)4

N

O

NH2O

O

4

NH

CH C

(CH2)4

O

NH2

HN CH C

CH2

N

OO

OO OH

H2N CH C

(CH2)4

N

O

NH2O

O

5

NH

N

O

O

3

N

O

OO

HO

O

H2N CH C

(CH2)4

N

O

NH2O

O

5

NH

N

O

O

NH

HC COOH

CH2

HOOC

O

O

HO

H2N CH C

(CH2)4

N

O

NH2O

O

NH

O

N

O

O

N

O

O

2

6

O

HO

H2N CH C

(CH2)4

N

O

NH2O

O

N

O

O

8

Sample G1

H2N CH C

(CH2)4

OH

O

NH2

L-Lys

H2N CH C

CH2

OH

O

C

OH

O

+

L-Asp

104 hours, H2SO4

1920 possible variants of structures, 9 possible structures were realized.

H2N CH C

(CH2)4

OH

O

NH2

H2N CH C

(CH2)4

O

NH2

HN CH C

(CH2)4

OH

O

NH2

L-Lys

Sample G1

HN CH C

(CH2)4

N

O

NH2O

O

N

O

O

CCHNH2

(CH2)4

O

NH2 n

n = 9

H2N CH C

(CH2)4

N

O

NH2O

O

N

O

O

13

H2N CH C

CH2

OH

O

C

OH

O

+

L-Asp

HN CH C

(CH2)4

N

O

NH2O

O

N

O

O

CCHNH2

(CH2)4

O

NH2 n

n = 8

19456 Possible variants of structures , 4 possible structures were realized.

278 hours, H2SO4

World of polypeptides

Page 34: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

World of polypeptides

Sample G3

H2N CH C

(CH2)4

OH

O

NH2

L-Lys

H2N CH C

CH2

OH

O

C

OH

O

+

L-Asp

860 Possible variants of structures , 11 possible structures were realized.

104 hours, HCl H2N CH C

(CH2)4

N

O

NH2O

O

N

O

O

3H2N CH C

(CH2)4

NH

O

NH2

NHO

O

HO

N

O

O

N

O

O

6O

O

HO

H2N CH C

(CH2)4

NH

O

NH2

N

O

O

N

O

O

6

O

O

HO

H2N CH C

(CH2)4

N

O

NH2O

O

NHO

O

HO

NH

O

O

N

O

OHO

NH

OHO

O OH

H2N CH C

(CH2)4

N

O

NH2O

O

NHO

O

HO

NHHC

O

OH(CH2)4

NH2

NH2-Lys-Asp-Asp-Lys-Asp-Asp-Asp-Lys-Asp-CO2H NH2-Lys-Lys-Asp-Asp-Asp-Asp-Asp-Lys-Asp-CO2H

NH2-Lys-Asp-CO2H

NH2-Lys-Asp-Asp-CO2H

NH2-Lys-Lys-Asp-CO2H

NH2-Lys-Lys-Asp-Asp-CO2H

Sample G3

H2N CH C

(CH2)4

OH

O

NH2

L-Lys

H2N CH C

CH2

OH

O

C

OH

O

+

L-Asp

128 Possible variants of structures , 4 possible structures were realized.

278 hours, HCl

H2N CH C

(CH2)4

N

O

NH2O

O

N

O

O

6

H2N CH C

(CH2)4

NH

O

NH2

N

O

O

N

O

O

5

O

O

HO

H2N CH C

(CH2)4

N

O

NH2O

O

NH

O

O

2

HO

N

O

O

2

NH

HC COOH

(CH2)4 NH2

NH2-Lys-Asp-COOH

Page 35: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Lys-Asp, basic solution

Chain 5 monomers: 9 structures of 60 possible

Chain 7 monomers: 11 structures of 252 possible

World of polypeptides

KK DK

DDK KDK KKK

DKDK KDKK DKDD

DKDDK DKKDK KDKKK

Page 36: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

All structures are closely related

Complimentary structures or intermediates

NH2-AspAspLys-COOH NH2-Asp-Asp-Lys-Asp-Asp-Asp-COOH

NH2-Asp-Asp-COOH NH2-Asp-Asp-Asp-Asp-COOH

NH2-Lys-Lys-COOH NH2-Lys-Lys-Lys-COOH

Page 37: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

General principles of evolution of multifunctional macromolecules

Non-statistical distribution of monomers along the polymeric chain

The primary synthesized polymers works as a template for sorption and subsequent polymerization

Selection factors (stability, catalysis, etc.)

A

X Y

B

X Y,

Termocycling

Evolution to unique structure, dramatic reduction of the number

of structural variants.

Page 38: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Globular peptides and proteins

Flexible polyanion RNA

Rigid-linear polyanion DNA

Interdependent coexistence of three worlds of pre-biopolymers

++

++

-

-

-

- -

-

-

-

-

-

-

-

-

Page 39: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

In the regime of hydrolytic degradation, system accumulates peptides and nucleic acids affine to each other and forming stable supramolecule complexes

Formation of stable suprmolecule complexes is a selective factor

k1 k2k3

Degradation

k1,k2> k3

Interdependent coexistence of three worlds of pre-biopolymers

Page 40: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Accumulation of selected limited repertoire of peptides (pre-proteins)

Accumulation of selected set of complexes of peptides with RNA

Transfer of structural information from RNA to peptide (and vice versa) and fixation in form of double-stranded DNA, molecular hieroglyphs

Polymer-RNAcomplex

RNA DNA DNA

Interdependent coexistence of three worlds of pre-biopolymers

Page 41: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

The same pattern for three main groups of biopolymers

Thermocycle (phase transfer (- H2O)) is a driving energetic force of the process and provides thermodynamics possibility of polycondensation

Autoselection of polymers composed of three-functional monomers. Polymer always makes influence on the products composition due to supramolecular interactions of monomers and polymers

This drives switch from statistical to evolutionary-driven synthesis

Proteins and peptides

RNA

DNA

Page 42: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

General principles of evolution of multifunctional macromolecules

(1) Non-statistical distribution of monomers along the polymeric chain

(2) The primary synthesized polymers work as the template for sorption and subsequent polymerization

(3) Selection (stability, catalysis, etc.)

A

X Y

B

X Y,

Termocycling

(4) Evolution to unic structure, dramatic reduction of the number

of structural variants.

Page 43: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Трифункциональные мономеры (X Y, X Y)

Предбиологическая эволюция биополимеров

Поликонденсация - базовый химический процесс (- H2O), образование амидов, пептидов, белков, фосфодиэфирной (РНК, ДНК) связи

Термоцикл (фазовый переход (- H2O)) – движущая энергитическая сила процесса – обеспечение термодинамической возможности поликонденсации

Page 44: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Предбиологическая эволюция биополимеров

Автоселекция полимеров из трифункциональных мономеров

Полимер ВСЕГДА оказывает влияние на состав продуктов в силу супрамолекулярного взаимодействия мономера с полимером

Переход от чисто статистического к эволюционно-направленному синтезу

Общие закономерности для всех трех основных классов биополимеров

- Пептиды и белки О , рибонуклеиновые кислоты (), дезоксирибонуклеиновые кислоты ( I I )

Page 45: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Большая термодинамическая устойчивость Большая устойчивость к гидролитической деструкции Каталитические свойства

Гидролиз пептидов Гидролиз полинуклеотидов Гидролиз пирофосфата Получение мономеров Поликонденсация аминокислот Поликонденсация нуклеотидов

Предбиологическая эволюция биополимеров

Принципы отбора(конкурентные преимущества)

Побеждает наиболее стабильный и «быстрый»

Page 46: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Подвижно – линейные - РНК

Жестко - линейные - ДНК

Взаимозависимое сосуществование трех «миров» предбиополимеров

Глобулярные – пептиды, белки

+ +

++-

--

-

--

-

--

--

-

-

Page 47: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Взаимозависимое сосуществование трех «миров» предбиополимеров

В режиме гидролитической

деградации в системе

накапливаются пептиды и

нуклеиновые кислоты, которые

афинны друг к другу, то есть

образуют устойчивые

супрамолекулярные комплексыОбразование стабильных супрамолекулярных комплексов как фактор отбора

+

k1

k2 k3

деградация

k1,k2> k3

Page 48: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Накапливается «отселектированный» ограниченный набор структур пептидов (предбелков)

Накапливается «отселектированный» набор комплексов пептидов – РНК

Перенос структурной информация от пептида к РНК, и «фиксация» этой информации в ДНК - форме

Взаимозависимое сосуществование трех «миров» предбиополимеров

+

Комплекс Полимер - РНК

РНК Цепь ДНК

ДвойнаяСпираль ДНК

Page 49: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Молекулярные иероглифы

Ферменты и активные центры ферментов Антитела Рецепторы Малые РНК

Page 50: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

The great paradox of enzymes origin

Very restricted number of catalytical sites structures

Page 51: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.
Page 52: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

2 Metal ions (2 Zn)\HDB Parathion hydrolase (1DPM)

Page 53: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Chymotrypsin and Streptogrisin

: Primary structures are absolutely different

Catalytical sites are the same

Page 54: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Organophosphatehydrolase

(EC 3..1.8.1)X

R2

P

R2

ZR3R1 O P OHR1 O + HZR3

H2O

Organophosphate hydrolase

O

X = O, S Z = O, S and F, when R3 is absent

Reaction catalyzed by

organophosphate hydrolase (EC 3.1.8.1)

Page 55: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

An important conclusion: The role of Asp from catalytic triad is to orient His, but not to serve as a proton relay

2.69Å

2.62Å

2.62Å

2.72Å

Asp102

Ser214

Ala55

Ser195

His57

X-ray structure 2PTC

Page 56: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Переход от гидролитических реакций к синтетическим-

Одни и те же каталитические структуры осуществляют гидролиз и синтез

Page 57: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

Structural Unity of catalytical sites

Pyrophosphatase Exonuclease DNA- polymerase

Page 58: N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia sdvarf@sky.chph.ras.ru Prebiological synthesis and evolution of macromolecules Sergey.

N.M. Emanuel Institute of Biochemical Physics, RAS, Moscow, Russia

[email protected]

Prebiological synthesis and evolution of macromolecules

S.D. Varfolomeev


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