Sphingolipid α‐Hydroxylase ( Scs7p )

Abstract

Abstract Sphingolipid α‐hydroxylase (Scs7p) is a membrane‐bound protein belonging to the hydroxylase/desaturase family of enzymes that utilize a dimetal center to hydroxylate or desaturate lipid‐based substrates. Scs7p specifically hydroxylates the α‐carbon of the very‐long‐chain fatty acid moiety of sphingolipid precursor molecules that are prevalent in the myelin sheath and epidermis, where they play a stabilizing role. The core structure of Scs7p consists of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum. Ten highly conserved histidine residues are responsible for coordinating the metal atoms within the core of the enzyme. Comparison of Scs7p structure and substrate‐binding model to the structure of stearoyl‐CoA desaturase reveals significant differences in the architecture of the enzymes within the catalytic cap domain. These differences provide insight into the different mechanisms of substrate binding and recognition of substrates by hydroxylase and desaturase enzymes.