4WXF : Crystal structure of L-Serine Hydroxymethyltransferase in complex with glycine

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:2.4
Classification:TRANSFERASE
Release Date:2015-02-04
Deposition Date:2014-11-13
Revision Date:2015-03-04#2017-09-13
Molecular Weight:93883.7
Macromolecule Type:Protein
Residue Count:856
Atom Site Count:6338
DOI:10.2210/pdb4wxf/pdb

Abstract:
α,α-Disubstituted α-amino acids are central to biotechnological and biomedical chemical processes for their own sake and as substructures of biologically active molecules for diverse biomedical applications. Structurally, these compounds contain a quaternary stereocenter, which is particularly challenging for stereoselective synthesis. The pyridoxal-5'-phosphate (PLP)-dependent L-serine hydroxymethyltransferase from Streptococcus thermophilus (SHMT(Sth); EC 2.1.2.1) was engineered to achieve the stereoselective synthesis of a broad structural variety of α,α-dialkyl-α-amino acids. This was accomplished by the formation of quaternary stereocenters through aldol addition of the amino acids D-Ala and D-Ser to a wide acceptor scope catalyzed by the minimalist SHMT(Sth) Y55T variant overcoming the limitation of the native enzyme for Gly. The SHMT(Sth) Y55T variant tolerates aromatic and aliphatic aldehydes as well as hydroxy- and nitrogen-containing aldehydes as acceptors.