Structure of Succinyl-CoA Synthetase

The crystal structure for Escherichia coli succinyl-CoA synthetase was determined at a resolution of 2.5 Å by using multiple isomorphous replacement x-ray crystallography in 1994. The researchers who did this published another article in 1999, in which they described the structure in greater detail, since they had refined the structure to a resolution of 2.3 Å. Succinyl-CoA synthetase is composed of one alpha subunit and one beta subunit, which interact with each other. The alpha subunit only interacts with the beta subunit, but two beta subunits interact to form a dimer of alpha-beta dimers. This interaction forms a functional heterotetramer in E. coli bacteria. There are two active sites that are formed at the sites where the alpha and beta subunits are in contact with each other. The other major difference between bacterial and mammalian SCS occurs here. While the bacterial SCS in a heterotetramer, mammalian SCS forms a dimer with only one alpha and one beta subunit. Because of this, there is also only one active site in mammalian SCS compared to the two active sites found in E. coli. In E. coli the alpha subunits are each composed of 288 amino acids and each has a molecular weight of 29.6 kDa. The beta subunits are each composed of 388 amino acids and each has a molecular weight of 41.4 kDa.

Both the alpha and beta subunits are composed of two types of helices and beta strands which are connected to each other by a series of loops. The alpha subunit is made up of ten helices and 14 beta strands. The beta strands are attached by loops and form two beta sheets which are mostly parallel. The sheets contain only one strand which is antiparallel. The sheets are surrounded by helices, which forms a doubly wound parallel beta sheet. This is a nucleotide binding motif. The helices are mainly alpha helical, with the exception of one which is a 310-helix. The beta subunit contains 15 helices. Two of these are 310-helices and the rest are alpha helices. The beta subunit also contains 19 beta strands, six of which comprise a mostly parallel beta sheet with one strand being antiparallel. This beta sheet is very similar to the beta sheets in the alpha subunit, and also forms a nucleotide binding motif. The main area of interaction between the alpha and beta subunits is found at the C-terminal domains of both the subunits. These are packed against each other and form the alpha-beta dimer.

SCS binds phosphate, CoA, succinate and/or succinyl-CoA. The phosphate and CoA can be found at in the interactive diagram below along with other aspect of the molecule discussed earlier on this page.

This button shows the alpha helices for ATP specific succinyl-CoA synthetase.

This button shows the beta sheets for ATP specific succinyl-CoA synthetase.

This button shows SCS in spacefill in relation to the ligands that are bound to it.

The molecular surface of the SCS heterotetramer associated with the ligands that are bound to it. (This button may take a while to execute.

You can click on the molecule to the right at any time and hold down the mouse button while dragging it and it allows you to rotate the molecule to see any of the angles that you would like.

Also, make sure that the buttons are pushed in order. If they aren't they won't work properly.

Structure