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

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A combined computational and experimental investigation of the [2Fe-2S] cluster in biotin synthase. / Fuchs, Michael G. G.; Meyer, Franc; Ryde, Ulf.

In: Journal of Biological Inorganic Chemistry, Vol. 15, No. 2, 2010, p. 203-212.

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T1 - A combined computational and experimental investigation of the [2Fe-2S] cluster in biotin synthase

AU - Fuchs, Michael G. G.

AU - Meyer, Franc

AU - Ryde, Ulf

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Quantum mechanics/molecular mechanics

KW - Radical S-adenosylmethionine enzyme

KW - Biotin synthase

KW - Fe/S cluster

KW - Quantum refinement

U2 - 10.1007/s00775-009-0585-6

DO - 10.1007/s00775-009-0585-6

M3 - Article

C2 - 19768473

VL - 15

SP - 203

EP - 212

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 1432-1327

IS - 2

ER -