INORGANIC CHEMISTRY
A closer mimic of the oxygen evolution complex of photosystem II and even photochemical reactions, but efficient biomimetic water oxidation catalysts based on Mn complexes have so far shown very limited success. In 2011, Agapie and coworkers synthesized a Mn3CaO4 cluster that structurally mimics the subsite of the OEC in PSII (12). However, the Mn4CaO4 cluster that Zhang et al. have synthesized has the core cubane structure Mn3CaO4 linked to a dangling Mn via one oxo bridge on the cubane (see the figure, panel B) and structurally mimics the full site of the OEC in PSII more closely. The x-ray crystal analysis of this synthetic Mn4CaO4 cluster revealed structural similarities to the OEC of PSII. First, both structures have the core cubane Mn3CaO4 and the dangling Mn atom. Second, for the first coordination sphere, both structures have one nitrogen-based ligand, with 6 carboxylates in the OEC and 10 carboxylates in the synthetic model. Third, the valence states of the Mn ions—Mn(III), Mn(IV), Mn(IV), and Mn(III)—are identical in both structures. The main difference in structural features is that in the OEC of PSII, there are
By Licheng Sun
T
“Making the synthetic models work as real water oxidation catalysts will require consideration of other structural features.”
he oxygen evolution complex (OEC) in photosystem II (PSII) catalyzes the photosplitting of water. The resulting electrons and protons are then ultimately used to create adenosine triphosphate to convert carbon dioxide (CO2) into organic compounds. An artificial catalyst that mimics the small inorganic OEC cluster within the much larger PSII stable S1 state. In this Mn4CaO5 cluster (see enzyme could be used to create fuels such the figure, panel A), five oxo-bridged O atas hydrogen from water via sunlight (1). Aloms form a twisted cubane with three Mn though tremendous efforts have been spent atoms and 1 Ca atom on the corners, and a on artificial photosynthesis systems (2), synfourth Mn atom outside the cubane held by thetic water oxidation catalysts that closely two of the five oxo bridges. Because one of mimic the structure and function of OEC in the oxo-bridged oxygens, O5, is much farther PSII have been very limited. Now, on page away from the Mn atoms than are the other 690 of this issue, Zhang et al. (3) describe the oxo-oxygen atoms, the O5 is likely a hydroxclosest structural mimic of the OEC in PSII ide ion instead of a normal oxygen dianion. reported to date. Thus, O5 may serve as one of the substrate The naturally occurring OEC contains O atoms and be involved in the O-O bond a cluster of manganese, calcium, and oxyformation step (9, 10). gen, Mn4CaO5. Several crystal structures Artificial molecular water oxidation cataof PSII have been reported since 2001 (4, lysts based on other transition metal com5), but these had insufficient resolution to plexes [for example, ruthenium (11)] can elucidate the atomic structure of the OEC. be very active in chemical, electrochemical, In 2011, Shen and co-workers reported a crystal structure of PSII at a resolution of 1.90 Å by x-ray Natural versus artificial diffraction using synchrotron raThe structure of the Mn4CaO5 cluster in photosystem II (A) (6) and the structure of the synthetic diation (6). Although much deMn4CaO5 cluster (B) prepared by the group of Zhang et al.; tBu is tert-butyl and Me is methyl. tailed structural information was revealed, extended x-ray absorption fine structure (EXAFS) studies t Bu A B t Bu showed that the Mn cations in the t Bu OEC are easily reduced (7), leading O O O to slight differences in the Mn-Mn O Tyr161 O t distances determined by different O Bu O O t techniques. Bu t His190 Bu Ca Very recently, Shen and collaboO N rators (8) used femtosecond x-ray Asp170 O1 O5’ Mn3+ O pulses to obtain a high-resolution O O O Ala344 O2 (1.95 Å) “radiation damage–free” O O O Ca O crystal structure of PSII in the darkO3 3+ 4+ 4+ O5
Mn
State Key Laboratory of Fine Chemicals, DUTKTH Joint Education and Research Center on Molecular Devices, Dalian University of Technology (DUT), Dalian 116024, China, and Department of Chemistry, KTH Royal Institute of Technology, 10044 Stockholm, Sweden. E-mail: [email protected]
Mn
Mn
O
O6 Mn
His322
Mn
O
Glu333
SCIENCE sciencemag.org
t
O
O
O Asp61
Ala342 Glu354
Mn
Mn
O4
Glu189
t
O Bu
t
Bu
O
Bu
t t
Bu
Bu =
Me Me Me
8 MAY 2015 • VOL 348 ISSUE 6235
Published by AAAS
635
Downloaded from www.sciencemag.org on May 8, 2015
An inorganic cluster replicates many of the structural aspects of the complex that photosplits water and powers photosynthesis
INSIGHTS | P E R S P E C T I V E S
REFERENCES AND NOTES
1. L. Sun, L. Hammarström, B. Åkermark, S. Styring, Chem. Soc. Rev. 30, 36 (2001). 2. M. D. Kärkäs, O. Verho, E. V. Johnston, B. Åkermark, Chem. Rev. 114, 11863 (2014). 3. C. Zhang et al., Science 348, 690 (2015). 4. A. Zouni et al., Nature 409, 739 (2001). 5. K. N. Ferreira, T. M. Iverson, K. Maghlaoui, J. Barber, S. Iwata, Science 303, 1831 (2004). 6. Y. Umena, K. Kawakami, J. R. Shen, N. Kamiya, Nature 473, 55 (2011). 7. J. Yano et al., Proc. Natl. Acad. Sci. U.S.A. 102, 12047 (2005). 8. M. Suga et al., Nature 517, 99 (2015). 9. N. Cox et al., Science 345, 804 (2014). 10. P. E. M. Siegbahn, Biochim. Biophys. Acta 1827, 1003 (2013). 11. L. Duan et al., Nat. Chem. 4, 418 (2012). 12. J. S. Kanady, E. Y. Tsui, M. W. Day, T. Agapie, Science 333, 733 (2011). ACKNOWLEDGMENTS
I thank L. Duan at KTH for assistance with the drawing of the figure. 10.1126/science.aaa9094
636
NEURODEVELOPMENT
“RASopathic” astrocytes constrain neural plasticity The cellular pathology of a complex neurodevelopmental disorder is teased apart By Lei Xing, Xiaoyan Li, William D. Snider
O
ver the past decade, mutations in genes encoding RAS family members, other components of an intracellular signaling cascade that RAS controls, and proteins that modify the cascade have been recognized as causes of developmental syndromes. Collectively, these syndromes are often referred to as “RASopathies.” Not surprisingly, RASopathies have numerous manifestations, including propensity to cancer, craniofacial abnormalities, cardiac defects, cutaneous abnormalities, neurodevelopmental delay, and varying degrees of cognitive dysfunction. Uncovering the causes and developing treatments for the neurodevelopmental abnormalities are a challenge because of the myriad cellular elements in the brain and the complexity of nervous system function. A recent study by Krencik et al. (1) takes a major step toward identifying the cellular pathology underlying Costello syndrome, a RASopathy that is characterized by delayed development, craniofacial and heart problems, and cognitive impairment. The latter appears to be linked to abnormal development and function of a population of nonneuronal cells (astrocytes) in the brain. The extracellular signal–regulated kinase/ mitogen-activated protein kinase (ERK/ MAPK) signaling cascade (also known as the RAS-RAF-MEK-ERK pathway) is among the most important cellular pathways, transducing effects of external signals and regulating key cellular responses such as proliferation, differentiation, and morphological development. Interestingly, most RASopathies exhibit gain of function in ERK signaling with exact clinical manifestations varying with Altering neural plasticity. Astrocytes derived from fibroblasts of Costello syndrome patients harboring the HRASG12S mutation exhibit premature differentiation, increased proliferation, and larger size compared to controls. They also express more extracellular matrix components, resulting in the formation of perineuronal nets around interneurons (in a mouse model of Costello syndrome). Premature formation of perineuronal nets may accelerate neuron maturity and “close” the critical period of plasticity.
the specific mutation (2). Dysregulation of ERK signaling in RASopathy mouse models leads to premature differentiation and overproduction of astrocytes (3, 4). Astrocytes and other glial cells, including oligodendroglia, are thought to represent more than 50% of the cellular elements in the human brain and are increasingly recognized as having important roles in regulating the development of brain circuits (5, 6). Hypertrophic astrocytes (mutant HRAS)
Oversecretion of extracellular matrix
Perineuronal net
Interneuron Premature closure of “critical period” for synaptic plasticity sciencemag.org SCIENCE
8 MAY 2015 • VOL 348 ISSUE 6235
Published by AAAS
ILLUSTRATION: V. ALTOUNIAN/SCIENCE
two oxo bridges (O5 and O6 in the figure, panel A) between the dangling Mn and the core cubane, but in the synthetic cluster there is only one oxo bridge (O5′ in the figure, panel B). The lack of the second oxo bridge (O6´) might be a fatal weakness for this synthetic model to work as a real catalyst for water oxidation. In the OEC of PSII, the O-O bond formation involves O5, and the second oxo bridge O6 can keep the dangling Mn at the correct position and redox potential after O5 has left during the O-O bond formation. In contrast, the dangling Mn in the synthetic model might detach from the core cubane after O5′ has left during the O-O bond formation if it follows a similar reaction pathway, which would inactivate the catalyst. Another difference is the lack of a potentially open coordination site in the synthetic model because of the short bond length between O5′ and the Mn (2.28 Å) on the corner of the core cubane, relative to the related bond length of 2.7 Å in the OEC of PSII. The work of Zhang et al. constitutes an important step toward a full structural mimic of the OEC in PSII. Further improvement of synthetic model complexes must address the second oxo bridge between the dangling Mn and the core cubane. Making the synthetic models work as real water oxidation catalysts will require consideration of other structural features. For example, longer distances between the corner Mn(III) and O5′, and between O5′ and the dangling Mn(III), need to be enforced via rational ligand design to provide a potentially open site for substrate water molecules to coordinate. This change also would allow the introduction of a pendent base in the second or third coordination sphere to facilitate the proton-coupled electron-transfer process during the O-O formation. ■
A closer mimic of the oxygen evolution complex of photosystem II Licheng Sun Science 348, 635 (2015); DOI: 10.1126/science.aaa9094
This copy is for your personal, non-commercial use only.
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here.
Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6235/635.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/348/6235/635.full.html#related This article cites 12 articles, 5 of which can be accessed free: http://www.sciencemag.org/content/348/6235/635.full.html#ref-list-1 This article appears in the following subject collections: Chemistry http://www.sciencemag.org/cgi/collection/chemistry
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on May 8, 2015
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A closer mimic of the oxygen evolution complex of photosystem II and even photochemical reactions, but efficient biomimetic water oxidation catalysts based on Mn complexes have so far shown very limited success. In 2011, Agapie and coworkers synthesized a Mn3CaO4 cluster that structurally mimics the subsite of the OEC in PSII (12). However, the Mn4CaO4 cluster that Zhang et al. have synthesized has the core cubane structure Mn3CaO4 linked to a dangling Mn via one oxo bridge on the cubane (see the figure, panel B) and structurally mimics the full site of the OEC in PSII more closely. The x-ray crystal analysis of this synthetic Mn4CaO4 cluster revealed structural similarities to the OEC of PSII. First, both structures have the core cubane Mn3CaO4 and the dangling Mn atom. Second, for the first coordination sphere, both structures have one nitrogen-based ligand, with 6 carboxylates in the OEC and 10 carboxylates in the synthetic model. Third, the valence states of the Mn ions—Mn(III), Mn(IV), Mn(IV), and Mn(III)—are identical in both structures. The main difference in structural features is that in the OEC of PSII, there are
By Licheng Sun
T
“Making the synthetic models work as real water oxidation catalysts will require consideration of other structural features.”
he oxygen evolution complex (OEC) in photosystem II (PSII) catalyzes the photosplitting of water. The resulting electrons and protons are then ultimately used to create adenosine triphosphate to convert carbon dioxide (CO2) into organic compounds. An artificial catalyst that mimics the small inorganic OEC cluster within the much larger PSII stable S1 state. In this Mn4CaO5 cluster (see enzyme could be used to create fuels such the figure, panel A), five oxo-bridged O atas hydrogen from water via sunlight (1). Aloms form a twisted cubane with three Mn though tremendous efforts have been spent atoms and 1 Ca atom on the corners, and a on artificial photosynthesis systems (2), synfourth Mn atom outside the cubane held by thetic water oxidation catalysts that closely two of the five oxo bridges. Because one of mimic the structure and function of OEC in the oxo-bridged oxygens, O5, is much farther PSII have been very limited. Now, on page away from the Mn atoms than are the other 690 of this issue, Zhang et al. (3) describe the oxo-oxygen atoms, the O5 is likely a hydroxclosest structural mimic of the OEC in PSII ide ion instead of a normal oxygen dianion. reported to date. Thus, O5 may serve as one of the substrate The naturally occurring OEC contains O atoms and be involved in the O-O bond a cluster of manganese, calcium, and oxyformation step (9, 10). gen, Mn4CaO5. Several crystal structures Artificial molecular water oxidation cataof PSII have been reported since 2001 (4, lysts based on other transition metal com5), but these had insufficient resolution to plexes [for example, ruthenium (11)] can elucidate the atomic structure of the OEC. be very active in chemical, electrochemical, In 2011, Shen and co-workers reported a crystal structure of PSII at a resolution of 1.90 Å by x-ray Natural versus artificial diffraction using synchrotron raThe structure of the Mn4CaO5 cluster in photosystem II (A) (6) and the structure of the synthetic diation (6). Although much deMn4CaO5 cluster (B) prepared by the group of Zhang et al.; tBu is tert-butyl and Me is methyl. tailed structural information was revealed, extended x-ray absorption fine structure (EXAFS) studies t Bu A B t Bu showed that the Mn cations in the t Bu OEC are easily reduced (7), leading O O O to slight differences in the Mn-Mn O Tyr161 O t distances determined by different O Bu O O t techniques. Bu t His190 Bu Ca Very recently, Shen and collaboO N rators (8) used femtosecond x-ray Asp170 O1 O5’ Mn3+ O pulses to obtain a high-resolution O O O Ala344 O2 (1.95 Å) “radiation damage–free” O O O Ca O crystal structure of PSII in the darkO3 3+ 4+ 4+ O5
Mn
State Key Laboratory of Fine Chemicals, DUTKTH Joint Education and Research Center on Molecular Devices, Dalian University of Technology (DUT), Dalian 116024, China, and Department of Chemistry, KTH Royal Institute of Technology, 10044 Stockholm, Sweden. E-mail: [email protected]
Mn
Mn
O
O6 Mn
His322
Mn
O
Glu333
SCIENCE sciencemag.org
t
O
O
O Asp61
Ala342 Glu354
Mn
Mn
O4
Glu189
t
O Bu
t
Bu
O
Bu
t t
Bu
Bu =
Me Me Me
8 MAY 2015 • VOL 348 ISSUE 6235
Published by AAAS
635
Downloaded from www.sciencemag.org on May 8, 2015
An inorganic cluster replicates many of the structural aspects of the complex that photosplits water and powers photosynthesis
INSIGHTS | P E R S P E C T I V E S
REFERENCES AND NOTES
1. L. Sun, L. Hammarström, B. Åkermark, S. Styring, Chem. Soc. Rev. 30, 36 (2001). 2. M. D. Kärkäs, O. Verho, E. V. Johnston, B. Åkermark, Chem. Rev. 114, 11863 (2014). 3. C. Zhang et al., Science 348, 690 (2015). 4. A. Zouni et al., Nature 409, 739 (2001). 5. K. N. Ferreira, T. M. Iverson, K. Maghlaoui, J. Barber, S. Iwata, Science 303, 1831 (2004). 6. Y. Umena, K. Kawakami, J. R. Shen, N. Kamiya, Nature 473, 55 (2011). 7. J. Yano et al., Proc. Natl. Acad. Sci. U.S.A. 102, 12047 (2005). 8. M. Suga et al., Nature 517, 99 (2015). 9. N. Cox et al., Science 345, 804 (2014). 10. P. E. M. Siegbahn, Biochim. Biophys. Acta 1827, 1003 (2013). 11. L. Duan et al., Nat. Chem. 4, 418 (2012). 12. J. S. Kanady, E. Y. Tsui, M. W. Day, T. Agapie, Science 333, 733 (2011). ACKNOWLEDGMENTS
I thank L. Duan at KTH for assistance with the drawing of the figure. 10.1126/science.aaa9094
636
NEURODEVELOPMENT
“RASopathic” astrocytes constrain neural plasticity The cellular pathology of a complex neurodevelopmental disorder is teased apart By Lei Xing, Xiaoyan Li, William D. Snider
O
ver the past decade, mutations in genes encoding RAS family members, other components of an intracellular signaling cascade that RAS controls, and proteins that modify the cascade have been recognized as causes of developmental syndromes. Collectively, these syndromes are often referred to as “RASopathies.” Not surprisingly, RASopathies have numerous manifestations, including propensity to cancer, craniofacial abnormalities, cardiac defects, cutaneous abnormalities, neurodevelopmental delay, and varying degrees of cognitive dysfunction. Uncovering the causes and developing treatments for the neurodevelopmental abnormalities are a challenge because of the myriad cellular elements in the brain and the complexity of nervous system function. A recent study by Krencik et al. (1) takes a major step toward identifying the cellular pathology underlying Costello syndrome, a RASopathy that is characterized by delayed development, craniofacial and heart problems, and cognitive impairment. The latter appears to be linked to abnormal development and function of a population of nonneuronal cells (astrocytes) in the brain. The extracellular signal–regulated kinase/ mitogen-activated protein kinase (ERK/ MAPK) signaling cascade (also known as the RAS-RAF-MEK-ERK pathway) is among the most important cellular pathways, transducing effects of external signals and regulating key cellular responses such as proliferation, differentiation, and morphological development. Interestingly, most RASopathies exhibit gain of function in ERK signaling with exact clinical manifestations varying with Altering neural plasticity. Astrocytes derived from fibroblasts of Costello syndrome patients harboring the HRASG12S mutation exhibit premature differentiation, increased proliferation, and larger size compared to controls. They also express more extracellular matrix components, resulting in the formation of perineuronal nets around interneurons (in a mouse model of Costello syndrome). Premature formation of perineuronal nets may accelerate neuron maturity and “close” the critical period of plasticity.
the specific mutation (2). Dysregulation of ERK signaling in RASopathy mouse models leads to premature differentiation and overproduction of astrocytes (3, 4). Astrocytes and other glial cells, including oligodendroglia, are thought to represent more than 50% of the cellular elements in the human brain and are increasingly recognized as having important roles in regulating the development of brain circuits (5, 6). Hypertrophic astrocytes (mutant HRAS)
Oversecretion of extracellular matrix
Perineuronal net
Interneuron Premature closure of “critical period” for synaptic plasticity sciencemag.org SCIENCE
8 MAY 2015 • VOL 348 ISSUE 6235
Published by AAAS
ILLUSTRATION: V. ALTOUNIAN/SCIENCE
two oxo bridges (O5 and O6 in the figure, panel A) between the dangling Mn and the core cubane, but in the synthetic cluster there is only one oxo bridge (O5′ in the figure, panel B). The lack of the second oxo bridge (O6´) might be a fatal weakness for this synthetic model to work as a real catalyst for water oxidation. In the OEC of PSII, the O-O bond formation involves O5, and the second oxo bridge O6 can keep the dangling Mn at the correct position and redox potential after O5 has left during the O-O bond formation. In contrast, the dangling Mn in the synthetic model might detach from the core cubane after O5′ has left during the O-O bond formation if it follows a similar reaction pathway, which would inactivate the catalyst. Another difference is the lack of a potentially open coordination site in the synthetic model because of the short bond length between O5′ and the Mn (2.28 Å) on the corner of the core cubane, relative to the related bond length of 2.7 Å in the OEC of PSII. The work of Zhang et al. constitutes an important step toward a full structural mimic of the OEC in PSII. Further improvement of synthetic model complexes must address the second oxo bridge between the dangling Mn and the core cubane. Making the synthetic models work as real water oxidation catalysts will require consideration of other structural features. For example, longer distances between the corner Mn(III) and O5′, and between O5′ and the dangling Mn(III), need to be enforced via rational ligand design to provide a potentially open site for substrate water molecules to coordinate. This change also would allow the introduction of a pendent base in the second or third coordination sphere to facilitate the proton-coupled electron-transfer process during the O-O formation. ■
A closer mimic of the oxygen evolution complex of photosystem II Licheng Sun Science 348, 635 (2015); DOI: 10.1126/science.aaa9094
This copy is for your personal, non-commercial use only.
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here.
Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6235/635.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/348/6235/635.full.html#related This article cites 12 articles, 5 of which can be accessed free: http://www.sciencemag.org/content/348/6235/635.full.html#ref-list-1 This article appears in the following subject collections: Chemistry http://www.sciencemag.org/cgi/collection/chemistry
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on May 8, 2015
The following resources related to this article are available online at www.sciencemag.org (this information is current as of May 7, 2015 ):
