Serine Dehydratase - Enzyme Structure

Enzyme Structure

HoloEnzyme: The holoenzyme SDH contains 319 residues, 1 PLP cofactor molecule, and 131 water molecules. The overall fold of the monomer is very similar to that of other PLP-dependent enzymes of the Beta-family. The enzyme contains a large domain (catalytic domain or PLP- binding domain) and a small domain. The domains are joined by two peptide linkers (residues 32-35 and 138-146), with the internal gap created being the space for the active site (Figure 1).

Figure 1 shows the large catalytic domain in purple and cyan and the small regulatory domain in green in a monomer of Serine Dehydratase. Two monomers(left and right) are shown and the coenzyme PLP is placed in the crevice between the two domains.

Two Dimers: Two monomers of hSDS (human SDH) come together to make a dimer. The interface between the two monomers is formed through hydrogen bonds and hydrophobic interactions. The monomer–monomer contacts involve six pairs of hydrogen bonds formed between 10 residues (Arg98-Asn260, Leu310-Asn260, and Leu265-Lys263). Additional interactions include a number of hydrophobic contacts between the residues Met17, Lys21, Asn101, Glu102, Ser306, Ile308, Ser309, and Ile264 in each monomer. (Figure 2).

Figure 2 shows the PLP coenzyme situated in the active site of SDH. The purple dashes are the hydrogen bonds involved. Top view of the enzyme.

Cofactor Binding Site: The PLP cofactor is positioned in between the Beta-strands 7 and 10 of the large domain and lies on the large internal gap made between small and large domain. The cofactor is covalently bonded through a Schiff base linkage to Lys41. The cofactor is sandwiched between the side chain of Phe40 and the main chain of Ala222. Each of the polar substituents of PLP is coordinated by functional groups: the pyridinium nitrogen of PLP is hydrogen-bonded to the side chain of Cys303, the C3-hydroxyl group of PLP is hydrogen-bonded to the side chain of Asn67, and the phosphate group of PLP is coordinated by main chain amides from the tetraglycine loop. (Figure 3 and Figure 4).

Figure 3 shows the hydrogen bonding in the active site of SDH. Hydrogen bonds are (red) between protein, water (blue balls) and the cofactor PLP (purple).

Figure 4 shows the alpha helices (pink) and beta sheets (yellow) involved in the secondary structure of SDH.