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The high-resolution structure of pig heart succinyl-CoA:3-oxoacid coenzyme A transferase
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Coker, Shu-Fen, Lloyd, Adrian J., Mitchell, Edward, Lewis, Gareth R., Coker, Alun R. and Shoolingin-Jordan, Peter M. (2010) The high-resolution structure of pig heart succinyl-CoA:3-oxoacid coenzyme A transferase. Acta Crystallographica Section D Biological Crystallography, Vol.66 (No.7). pp. 797-805. doi:10.1107/S0907444910018366 ISSN 0907-4449.
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Official URL: http://dx.doi.org/10.1107/S0907444910018366
Abstract
The enzyme succinyl-CoA:3-oxoacid coenzyme A transferase (SCOT) participates in the metabolism of ketone bodies in extrahepatic tissues. It catalyses the transfer of coenzyme A (CoA) from succinyl-CoA to acetoacetate with a classical ping-pong mechanism. There is biochemical evidence that the enzyme undergoes conformational changes during the reaction, but no domain movements have been reported in the available crystal structures. Here, a structure of pig heart SCOT refined at 1.5 angstrom resolution is presented, showing that one of the four enzyme subunits in the crystallographic asymmetric unit has a molecule of glycerol bound in the active site; the glycerol molecule is hydrogen bonded to the conserved catalytic glutamate residue and is likely to occupy the cosubstrate-binding site. The binding of glycerol is associated with a substantial relative movement (a 13 degrees rotation) of two previously undefined domains that close around the substrate-binding site. The binding orientation of one of the cosubstrates, acetoacetate, is suggested based on the glycerol binding and the possibility that this dynamic domain movement is of functional importance is discussed.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > Q Science (General) | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Acta Crystallographica Section D Biological Crystallography | ||||
| Publisher: | Wiley-Blackwell Publishing, Inc. | ||||
| ISSN: | 0907-4449 | ||||
| Official Date: | 2010 | ||||
| Dates: |
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| Volume: | Vol.66 | ||||
| Number: | No.7 | ||||
| Number of Pages: | 9 | ||||
| Page Range: | pp. 797-805 | ||||
| DOI: | 10.1107/S0907444910018366 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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