Química Bioinorganic básica de Manganeso en todo...

Química Bioinorganic básica de Manganeso en todo

a fotosíntesis

1

Los Colores de Vida

CURSO QUÍMICA BIOINORGÁNICA

UNAM Octobre 24/29, 2012

PETER M.H. KRONECK, Lab 212

peter.kroneck@uni-konstanz.de

Artículos que introducen R.R. Crichton (2008)

Biological Inorganic Chemistry (chapter 16). Elsevier.

C.F Yocum, V.L Pecoraro (1999)

Current Opinion in Chemical Biology, 3,182-l 87Recent advances in the understanding of

the biological chemistry of manganese

A.J. Wu , J.E. Penner-Hahn, V.L. Pecoraro (2004)

Chemical Reviews, 104, 908-938. Structural, Spectroscopic, and Reactivity Models for the

Manganese Catalases

J.P. McEvoy, G.W. Brudvig (2006)

Chemical Reviews, 106, 4455-4483. Water-Splitting Chemistry of Photosystem II

T. M Iverson (2006)

Current Opinion in Chemical Biology, 10, 91–100. Evolution and unique bioenergetic

mechanisms in oxygenic photosynthesis

J. Barber (2006)

Biochemical Society Transactions, 34, 619-631. Photosystem II: an enzyme of global

significance

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html

http://www.phschool.com/science/biology_place/biocoach/photosynth/overview.html

2

Repetición: ROS = Reactive Oxygen Species

Especies de Oxígeno reactivas

ss

ss*

sp*

sp

p*

p

3S+

O2

O•2-

H2O2

OH•+H2O

2H2O

-0.33V

+0.94V

+0.38V

+2.31V

E‘o vs NHE, pH 7.25

112 pm

133 pm

149 pm

1554 cm-1

1145 cm-1

842 cm-1

3

Conservación de la energía de hoy: Reducción de O2 a H2O

Gente es Aerobes

4

Los elementos de vida www.webelements.com

Abundancia en el cuerpo (75 kg)

Ca: 1.2 kg

K: 150 g

Na: 70 g

Mg: 20-30 g

Fe: 4-7 g

Zn: 2-3 g

Cu: 70-100 mg

Mn: 10-12 mg

S: 140 g

P: 780 g

H He

Li Be B C N O F Ne

Na Mg Al Si P S Cl Ar

K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr

Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe

Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn

5

Metales de transición - Funciones Biológicas Na Charge Carrier, Osmolysis/equilibrium

K Charge Carrier, Osmolysis/equilibrium

Mg Structure, ATP/ThDP Binding, Photosynthesis,...

Ca Structure, Signaling, Charge Carrier

V Nitrogen Fixation, Oxidases, O2 Carrier

Cr Unknown! (glucose metabolism ???)

Mo Nitrogen Fixation, Oxidoreductase, O-Transfer

W Oxidoreductases, Acetylene Hydratase

Mn REDOX/ACID-BASE CATALYSIS

Photosynthesis, Oxidases, Structure,...

Fe Oxidoreductase, O2 Transport + Activation,e--Transfer,...

Co Oxidoreductase, Vitamin B12 (Alkyl Group Transfer)

Ni Hydrogenase, CO Dehydrogenase, Hydrolases, Urease

Cu Oxidoreductases, O2 Transport, e- -Transfer

Zn Structure, Hydrolases, Acid-Base Catalysis... 6

Estados de oxidación de Metales de Transición Na Na(I)

K K(I)

Mg Mg(II)

Ca Ca(II)

V V(V)=(d0), V(IV)=(d1), V(III)=(d2)

Cr Cr(III)=(d3),Cr(IV)=(d2),Cr(V)=(d1)

Mo Mo(III)=(d3),Mo(IV)=(d2),Mo(V)=(d1), Mo(VI)=(d0)

W W(IV)=(d2) ,W(V) =(d1), W(VI)=(d0)

Mn Mn(IV)=(d3), Mn(III)=(d4), Mn(II) =(d5)

Fe Fe(V)=(d3), Fe(IV)=(d4),Fe(III)=(d5),Fe(II)=(d6), Fe(I)?=(d7)

Co Co(III)=(d6), Co(II)=(d7), Co(I)=(d8)

Ni Ni(III)=(d7), Ni(II)=(d8), Ni(I)=(d9)

Cu Cu(III)=(d8), Cu(II)=(d9), Cu(I)=(d10)

Zn Zn(II) =(d10) 7

Mn Biochemistry R.R. Crichton, Chap. 16

8

The importance of Mn for living organisms is considerable:

(i) the tetranuclear Mn cluster involved in O2 production in photosynthetic

plants, algae and cyanobacteria

(ii) mammalian enzymes, arginase and mitochondrial superoxide dismutase.

(iii)Most of Mn biochemistry can be explained by its redox activity, and by

its analogy to Mg2+.

In contrast to other redox active metals (Fe) is that Mn is less reducing than

Fe under most biological conditions; Fe3+ is stable relative to Fe2+, Mn2+

relative to Mn3+ (Why ?). Two important consequences of this redox

chemistry are that Mn2+ can participate in useful redox catalysis on many

similar substrates to Fe3+, whereas the higher redox potential of Mn2+ makes

free Mn2+ harmless under conditions where free Fe2+ would produce

hydroxyl radicals. Cells (notably bacterial cells) can tolerate very high

cytoplasmic concentrations of Mn2+ with no negative consequences; this is

certainly not the case with redox metal ions like Fe and Cu.

Bioquímica de Mn R.R. Crichton, Chap. 16

9

La importancia de Mn para organismos vivos es considerable:

(i) el Mn tetranuclear cluster que está implicado en la producción de oxígeno en

fábricas fotosintéticas, algas y cyanobacteria

(ii) enzimas mamíferas como arginase y superóxido mitochondrial dismutase.

(iii) la mayor parte de la bioquímica de Mn puede ser explicada por su actividad

redox, y en otro por su analogía con Mg2+.

En contraste con otros metales activos redox (Fe) es que Mn tiene el potencial

menos que reduce que Fe en la mayor parte de condiciones biológicas; Fe3+ es

estable con relación a Fe2+, Mn2+ con relación a Mn3+ (Por qué ?). Dos

consecuencias importantes de esta química redox son que Mn2+ puede

participar en la catálisis redox útil en muchos substrates similares a Fe3+,

mientras que más alto redox potencial de Mn2+ hace Mn2+ libre inocuo en

condiciones donde liberado Fe2+ produciría a radicales hydroxyl. Las células

(notablemente células bacterianas) pueden tolerar concentraciones

citoplásmicas muy altas de Mn2+ sin consecuencias negativas; esto no es

seguramente el caso con iones metálicos redox como Fe y Cu.

Mn Biochemistry R.R. Crichton, Chap. 16

10

Mn is the cofactor for superoxide dismutases, catalases and some

peroxidases. These enzymes are all used for the detoxification of

ROS.

An important property of Mn in its (2+)-oxidation state, which has

important consequences, is that is a close but not exact surrogate of

Mg2+. Mn2+ with its relatively similar ionic radius can readily

exchange with Mg2+ in most structural environments, and exhibits

much of the labile, octahedral coordination chemistry. However, it can

more easily accommodate the distortions in coordination geometry in

progressing from the substrate-bound to the transition state and to the

bound product. Consequently, Mn2+ in the active site of a Mg2+-

enzyme often results in improved enzyme efficacy.

Mn Biochemistry R.R. Crichton, Chap. 16

11

Mn es el cofactor para el superóxido dismutases, catalases y algún

peroxidases. Estas enzimas son todos usadas para el detoxification de

ROS.

Una propiedad importante de Mn en su (2+) estado de oxidación, que

tiene consecuencias importantes, es un final, pero no sustituto exacto

de Mg2+. Mn2+ con su radio iónico relativamente similar puede

cambiar fácilmente con Mg2+ en la mayor parte de ambientes

estructurales, y expone la mayor parte de los labile, octahedral

química de coordinación. Sin embargo, esto puede acomodar más

fácilmente la deformación en la geometría de coordinación en la

progresión del substrate-ligado al estado de transición y al producto

atado. Por consiguiente, Mn2+ con el sitio activo de un Mg2+-enzyme a

menudo causa la eficacia de enzima mejorada.

Estimated evolution of atmospheric O2

The red and green lines represent the range of the estimates: stage1: 3.85–2.45 Gyr (Ga),

stage2: 2.45–1.85 Ga, stage3: 1.85–0.85 Ga, stage4: 0.85–0.54Ga, stage5: 0.54 Ga–present www.globalchange.umich.edu/globalchange1/current/lectures/Perry_Samson_lectures/evolution_atm/index.html

H.D. Holland (2006), Phil. Trans. R. Soc. B, 361, 903-915

Formas de Vida – De Anaerobio a Aerobio

condiciones anóxicas (-O2) contra condiciones óxicas (+O2)

12

Activación de O2 – Tipos de Reacción

• Reversible binding of O2 – Myoglobin, Hemoglobin (Fe), Hemocyanin

(Cu-Cu)

• O2.- dismutation – Superoxide Dismutase (Mn, Fe, Ni, Cu, Zn)

O2.- + O2

.- +2H+ → O2 + H2O2

• H2O2 decomposition – Catalase (Mn, heme-Fe)

2 H2O2 → 2 H2O + O2

• Oxygenases (Mn, Fe, Cu, Cytochrome P450)

R-H + O2 + NADPH + H+ → R-OH + H2O + NADP+

• Oxidases (2-electron reduction to H2O2; Fe, Cu)

O2 + 2e- +2H+ → H2O2 (focus on Cu enzyme Galactose Oxidase)

• Oxidases (4-electron reduction to H2O; heme-Fe, Cu)

O2 + 4e- +4H+ → 2 H2O (focus on Cu enzyme Ascorbic Acid Oxidase

and Fe,Cu enzyme Cytochrome c Oxidase)

13

No proteína Ligantes

Ligand pKa

Acid/base H2O/OH-,O2- 14,~34

HCO3-/CO3

2- 10.3

HPO42-/PO4

3- 12.7

H3CCOO-/H3CCOOH 4.7

HO2- /H2O2 11.6

NH3 /NH4+ 9.3

N3- /N3H

4.8

F-, Cl- Br-, I-/XH 3.5, -7, -9, -11

Neutral O2, CO, NO, RNC

Mn+ O

H

H

d-

d+

d+

14

Modulación de acidez (pKa)

H2O + Mn+ HO- -Mn+ -H+

+H+

Metal pKa

none Ca2+

Mn2+

Cu2+

Zn2+

14.0 13.4

11.1

10.7

10.0

4 orders of

magnitude !

Mn+ O

H

H

d-

d+

d+ 15

Control cinético

[Mn+(H2O)m] -H2O

+H2O

[Mn+(H2O)m-1]

Metal k (s-1)

K+

Ca2+

Mn2+

Fe2+

Ni2+

1x109

3x108

2x107

4x106

4x104

15 orders of

magnitude!

Fe3+ 2x102

Co2+ 3x106

Co3+ <10-6 16

17

Velocidades de cambio acuáticos M. Eigen, Nobel Prize Lecture 1967

Expresado como vida de complejos

Útil para mirar la reactividad en

ligand cambian reacciones - catálisis

inert labile

18

Estabilidad de Complejos de Ión Metálicos:

Irving-Williams Series

Stability order for high-spin divalent metal ion

complexes: Peak at Cu(II), Minimum at Mn(II)

Proteína Ligantes – Residuos de Aminoácido

Mn prefiere ligar el oxígeno ligantes N O S

His

Lys

Tyr

Glu(+Asp)

Ser

Cys

Met

19

La superposición de estructura del metal se centra en in Fe-

homoprotocatechuate 2,3-dioxygenase (PDB 2IG9) y Mn-HPCD

(PDB 3BZA) Atoms: gray C; blue N; red O; magenta Mn

J.P. Emerson et al. (2008) PNAS, 105, 7347–7352

20

Humano Mn SOD Tetramer Borgstahl et al. (1996) Biochemistry, 35, 4287-4297; Quint et al. (2006) Biochemistry, 45,

8209–8215

21

Mn SOD PDB 1VAR

http://en.wikipedia.org/wiki/Superoxide_dismutase

22

The dismutation of superoxide

may be written as:

M(n+1)+-SOD + O2− → Mn+-

SOD + O2

Mn+-SOD + O2− + 2H+ →

M(n+1)+-SOD + H2O2.

M = Cu (n=1); Mn (n=2) ; Fe

(n=2) ; Ni (n=2).

The oxidation state of the

metal cation oscillates between

n and n+1.

El sitio activo de Lactobacillus plantarum Mn-catalase

(Hexamer, PDB 1JKV and 1JKU; V.V. Barynin et al.(2001), Structure, 2001, 9, 725–738)

23

2 H2O2 → 2 H2O + O2

Azide (N3-) ligando en el sitio activo de Lactobacillus

plantarum Mn-catalase

24

Mn Ribonucleotide Reductase J.E. Martin, J.A. Imlay (2011), Mol Microbiol., 80, 319–334; J.A. Stubbe, J. A. Cotruvo

(2011), Curr Opin Chem Biol., 15, 284–290

25

Ribonucleotide Reductase Chemistry http://en.wikipedia.org/wiki/Ribonucleotide_reductase

26

Química Bioinorganic básica de Manganeso en todo a fotosíntesis

Luz conducida en evolución de dioxygen

27

A.W. Rutherford, A. Boussac (2004) Science, 303, 1782-1784; S. Merchant, M. Sawaya (2005) Plant cell 17, 648-663; D. A. Bryant, N.-U. Frigaard (2006) TRENDS in Microbiology, 14, 488-496; T. M. Iverson (2006) Current Opinion in Chemical Biology , 10, 91–100; D.G. Nocera (2012) ACCOUNTS OF CHEMICAL RESEARCH, 45, 767–776.

Introducción a Fotosíntesis (Britannica Enciclopedia en Línea)

http://www.britannica.com/EBchecked/topic/458172/photosynthesis

28

O2 Evolving Complex (OEC), a Mn4CaO5

Cluster

BaMn8O16

Punto para recordar: Relase de oxígeno, la

respuesta puede ser encontrada en las rocas Mineral Hollandite:

Ba0.8Pb0.2Na0.1Mn4+6.1Fe3+

1.3Mn2+0.5Al0.2Si0.1O16

29

(a) End-on view of the Hollandite lattice (tunnel

type) consisting of Mn (red) and O (blue) atoms and showing the proposed location of Ba2+ cations (gray) in the 2 × 2 tunnels (57, 58).

There are two kinds of bridging O atoms, and one of each kind is designated by vertical stripes (sp3-

like) or horizontal stripes (sp2-like). (b) Oblique view of the hollandite lattice shows the difference in the mode of bridging of the sp3-like (apical) and sp2-like (planar) O atoms between three Mn atoms.

(c) Expanded oblique view shows more clearly the differences between the sp3-like (vertical stripes) and sp2-like (horizontal stripes) bridging O atoms.

Sauer K , Yachandra VK (2002) PNAS, 99, 8631-8636

©2002 by National Academy of Sciences 30

El centro de reacción Fotosintético (PS I) de bacterias moradas

Luz conducida en síntesis de ATP (C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

31

Robert Huber, Premio Nobel

1988 (con Deisenhofer y

Michel)

El centro de reacción Fotosintético (PS I) de bacterias moradas (C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

32

El centro de reacción Fotosintético de bacterias moradas y

Transferencia electrónica (C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

33

Módulos fundamentales del Aparato de Fotosíntesis Light-dependent reactions of photosynthesis at the thylakoid membrane

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html

http://www.phschool.com/science/biology_place/biocoach/photosynth/intro.html

http://en.wikipedia.org/wiki/Photosynthesis

34 34

Respiración de Mitochondrial & Síntesis de Centro de Reacción

Fotosintética de ATP – transferencia de electrón/protón

Conectada – fuerza de Protonmotive

35

Módulos fundamentales del Aparato de Fotosíntesis The "Z scheme"

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html

http://www.phschool.com/science/biology_place/biocoach/photosynth/intro.html

http://en.wikipedia.org/wiki/Photosynthesis

36

3D estructura de Fotosistema II de alga Synechococcus elongatus

(3.8 Å resolution, Zouni et al. (2001), NATURE, 409, 739)

37

Cofactors de Fotosistema de Photosystem II (Synechococcus elongatus)

(water-oxidizing, OEC = oxygen-evolving complex, a 4 Mn cluster)

38

Estructura de Clorofila. La estructura de clorofila b es mostrada con la Unión internacional de enumeración de Química Pura y Aplicada

Merchant S, Sawaya M. Plantcell 2005;17:648-663 ©2005 by American Society of Plant Biologists

39

Chlorophyll (Mg) y Heme (Fe)

40

Porphyrin ring y Phytol chain

La oxidación de la agua, complejo que desarrolla el oxígeno,

un 3Mn+1Mn cluster ???

41

Y Umena et al. Nature (2011) doi:10.1038/nature09913

Estructura total de PSII dimer de T. vulcanus en una

resolución de 1.9 Å Umena1 et al. (2011), Nature, 473, 55-60

42

Y Umena et al. Nature (2011) doi:10.1038/nature09913

Organización de chlorophylls

43

Y Umena et al. Nature (2011) doi:10.1038/nature09913

Structure of the Mn4CaO5 cluster (OEC).

44

The Mn4CaO5 Cluster (OEC)

45

Y Umena et al. Nature (2011) doi:10.1038/nature09913

Hydrogen-bond network around YZ.

46

The S-state (Kok) cycle showing how the absorption of four photons of light (hν) by

P680 drives the splitting of two water molecules and formation of O2 through a

consecutive series of five intermediates (S0, S1, S2, S3, and S4). The S-states

represent the various oxidation states of Mn in PSII-OEC. Electron donation from

the PSII-OEC to P680•+ is mediated by tyrosine, YZ.

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

47

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

La Hoja artificial

48

The solar photons are stored by photosynthesis to split water to oxygen and four

protons and four electrons, which are utilized in the conversion of carbon

dioxide to carbohydrates.

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

49

A simplified scheme of the light-driven reactions of photosynthesis. Solar photons

create a wireless current that is harnessed by redox cofactors at the terminus of the

charge-separating network to translate the wireless current into a solar fuel by

performing the water splitting reaction at OEC. The initial reductant, plastoquinol

(PQH2), is translated into NADPH in PSI, which transfers “hydrogen” to the Calvin

cycle where it is fixed with CO2 to produce carbohydrates.

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

50

(left) Schematic of cubane structure of PSII-OEC. (middle) Structure of the Co-

OEC as determined from EXAFS (Pi not shown). Co-OEC is the head-to-tail

dimer of the cubane of PSII-OEC. (right) Co-OEC structure rotated by 45° to

more clearly shows edge sharing octahedra. The alkali metal ions, which are not

shown, likely reside above the 3-fold triangle defined by the μ-bridging oxygens.

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

51

Proposed pathway for water splitting by Co-OEC. A PCET equilibrium proceeds

the turnover-limiting O–O bond-forming step. Curved lines denote phosphate or

terminal oxygen (from water or hydroxide). The oxyl radical in the far right

structure is shown for emphasis. If the hole is completely localized on oxygen,

then the Co oxidation state is Co(III) and not Co(IV).

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

52

Schematic of a Co-OEC functionalized npp+-silicon single-junction PEC cell.

The buried junction performance characteristics are Isc = 26.7 mA/cm2 and Voc

= 0.57 V.

Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.

DOI: 10.1021/ar2003013

Copyright © 2012 American Chemical Society

53

Resumen – Viviendo en una Mundo de Oxígeno

Respiración & Fotosíntesis (energy conservation – ATP synthesis – proton-coupled-electron transfer)

• The use of the electron acceptor dioxygen and the photosynthetic production of dioxygen (water-oxidizing, oxygen-evolving complex) are two elementary processes of life which depend on a complex network of multi-site proteins and enzymes. Redox and light driven reactions are used for energy conservation (proton pumping; ATP synthesis).

• The 3Cu-2Fe, multi-subunit enzyme cytochrome c oxidase is the terminal oxidase of mitochondrial respiration, whereas the Mn4CaO5 cluster (with a tyrosine nearby) constitutes the oxygen evolving complex.

• The reduction of dioxygen to water proceeds without the release of ROS. COX receives the electrons via cytochrome c from where they are transferred to the dinuclear mixed valence electron transfer center CuA.

• The dinuclear heme-CuB center constitutes the reduction site of dioxygen, which carries a covalently attached tyrosine at the active site.

54

Resumen – Viviendo en una Mundo de Oxígeno

Respiración & Fotosíntesis (energy conservation – ATP synthesis – coupled electron-proton transfer)

• COX represents a redox driven proton pump, with defined electron and proton transfer pathways (redox protons vs protons).

• The mechanism of dioxygen reduction is relatively well understood, its mechanism has been characterized both by spectroscopic and structural techniques at high resolution. It appears that a tyrosine (radical), in addition to Fe and Cu centers, is involved in catalysis.

• The dioxygen production (PS II) is a light-driven metalloradical enzyme process. The splitting of water and formation of dioxygen at the Mn4CaO5 cluster is still less understood despite a huge amount of spectroscopic and biochemical studies. For Mn, cycling between oxidation states +2, +3, and +4, has been suggested (S-state model).

• New techniques have been employed to grow better crystals of these extremely large membrane-bound molecules to achieve a resolution below 2 Å, to understand their function on an atomic level.

55