5x5h

Publication Abstract from PubMed

Cystathionine gamma-synthase (MetB) condenses O-acetyl-l-homoserine (OAHS) or O-succinyl-l-homoserine (OSHS) with cysteine to produce cystathionine. To investigate the molecular mechanisms and substrate specificity of MetB from Corynebacterium glutamicum (CgMetB), we determined its crystal structure at 1.5 A resolution. The pyridoxal phosphate cofactor is covalently bound to Lys204 via a Schiff base linkage in the deep cavity. Superposition with the structure of MetB from Nicotiana tabacum in complex with its inhibitor dl-(E)-2-amino-5-phosphono-3-pentenoic acid revealed that Thr347 from the beta10-beta11 connecting loop, located at the entrance of the active site, is speculated to be a main contributor for stabilization of the acetyl group of OAHS. Moreover, on the basis of structural comparison of CgMetB with EcMetB utilizing OSHS as a main substrate, we propose that the conformation of the beta10-beta11 connecting loops determines the size and shape of the acetyl- or succinyl-group binding site and ultimately determines the substrate specificity of MetBs toward OAHS or OSHS.

Structural Insights into Substrate Specificity of Cystathionine gamma-Synthase from Corynebacterium glutamicum.,Sagong HY, Kim KJ J Agric Food Chem. 2017 Jul 26;65(29):6002-6008. doi: 10.1021/acs.jafc.7b02391., Epub 2017 Jul 13. PMID:28675039^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.