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A combined computational and experimental investigation of the [2Fe-2S] cluster in biotin synthase

Fuchs, Michael G. G.; Meyer, Franc and Ryde, Ulf LU (2010) In Journal of Biological Inorganic Chemistry 15(2). p.203-212
Abstract
Biotin synthase was the first example of what is now regarded as a distinctive enzyme class within the radical S-adenosylmethionine superfamily, the members of which use Fe/S Clusters as the sulphur source in radical sulphur insertion reactions. The crystal structure showed that this enzyme contains a [2Fe-2S] cluster with a highly unusual arginine ligand, besides three normal cysteine ligands. However, the crystal structure is at such a low resolution that neither the exact coordination mode nor the role of this exceptional ligand has been elucidated yet, although it has been shown that it is not essential for enzyme activity. We have used quantum refinement of the crystal structure and combined quantum mechanical and molecular mechanical... (More)
Biotin synthase was the first example of what is now regarded as a distinctive enzyme class within the radical S-adenosylmethionine superfamily, the members of which use Fe/S Clusters as the sulphur source in radical sulphur insertion reactions. The crystal structure showed that this enzyme contains a [2Fe-2S] cluster with a highly unusual arginine ligand, besides three normal cysteine ligands. However, the crystal structure is at such a low resolution that neither the exact coordination mode nor the role of this exceptional ligand has been elucidated yet, although it has been shown that it is not essential for enzyme activity. We have used quantum refinement of the crystal structure and combined quantum mechanical and molecular mechanical calculations to explore possible coordination modes and their influences on Cluster properties. The investigations show that the protonation state of the arginine ligand has little influence on cluster geometry, so even a positively charged guanidinium moiety would be in close proximity to the iron atom. Nevertheless, the crystallised enzyme most probably contains a deprotonated (neutral) arginine coordinating via the NH group. Furthermore, the Fe center dot center dot center dot Fe distance seems to be independent of the coordination mode and is in perfect agreement with distances in other structurally characterised [2Fe-2S] clusters. The exceptionally large Fe center dot center dot center dot Fe distance found in the crystal structure could not be reproduced. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Quantum mechanics/molecular mechanics, Radical S-adenosylmethionine enzyme, Biotin synthase, Fe/S cluster, Quantum refinement
in
Journal of Biological Inorganic Chemistry
volume
15
issue
2
pages
203 - 212
publisher
Springer
external identifiers
  • wos:000274742000008
  • scopus:77949272771
ISSN
1432-1327
DOI
10.1007/s00775-009-0585-6
language
English
LU publication?
yes
id
b297c915-76e6-40f1-9754-021ccc2c26b2 (old id 1568542)
date added to LUP
2010-03-23 12:32:47
date last changed
2018-05-29 10:29:52
@article{b297c915-76e6-40f1-9754-021ccc2c26b2,
  abstract     = {Biotin synthase was the first example of what is now regarded as a distinctive enzyme class within the radical S-adenosylmethionine superfamily, the members of which use Fe/S Clusters as the sulphur source in radical sulphur insertion reactions. The crystal structure showed that this enzyme contains a [2Fe-2S] cluster with a highly unusual arginine ligand, besides three normal cysteine ligands. However, the crystal structure is at such a low resolution that neither the exact coordination mode nor the role of this exceptional ligand has been elucidated yet, although it has been shown that it is not essential for enzyme activity. We have used quantum refinement of the crystal structure and combined quantum mechanical and molecular mechanical calculations to explore possible coordination modes and their influences on Cluster properties. The investigations show that the protonation state of the arginine ligand has little influence on cluster geometry, so even a positively charged guanidinium moiety would be in close proximity to the iron atom. Nevertheless, the crystallised enzyme most probably contains a deprotonated (neutral) arginine coordinating via the NH group. Furthermore, the Fe center dot center dot center dot Fe distance seems to be independent of the coordination mode and is in perfect agreement with distances in other structurally characterised [2Fe-2S] clusters. The exceptionally large Fe center dot center dot center dot Fe distance found in the crystal structure could not be reproduced.},
  author       = {Fuchs, Michael G. G. and Meyer, Franc and Ryde, Ulf},
  issn         = {1432-1327},
  keyword      = {Quantum mechanics/molecular mechanics,Radical S-adenosylmethionine enzyme,Biotin synthase,Fe/S cluster,Quantum refinement},
  language     = {eng},
  number       = {2},
  pages        = {203--212},
  publisher    = {Springer},
  series       = {Journal of Biological Inorganic Chemistry},
  title        = {A combined computational and experimental investigation of the [2Fe-2S] cluster in biotin synthase},
  url          = {http://dx.doi.org/10.1007/s00775-009-0585-6},
  volume       = {15},
  year         = {2010},
}