Ohgusu Hideko, Takahashi Tomoko, Kojima Masayasu
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan.
Methods Enzymol. 2012;514:147-63. doi: 10.1016/B978-0-12-381272-8.00010-6.
Ghrelin is a gastric peptide hormone in which serine 3 (threonine 3 in frogs) is modified primarily by an n-octanoic acid; this modification is essential for ghrelin's activity. The enzyme that transfers n-octanoic acid to the third serine residue of ghrelin peptide has been identified and named GOAT for ghrelin O-acyltransferase. GOAT is the only known enzyme that catalyzes the acyl modification of ghrelin and specifically modifies the third amino acid serine and does not modify other serine residues in ghrelin peptides. GOAT prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach n-octanoyl form is the main acyl-modified ghrelin and the concentration of n-hexanoyl form is very low. Moreover, a four-amino acid peptide derived from the N-terminal sequence of ghrelin can be modified by GOAT, indicating that these four amino acids constitute the core motif for substrate recognition by the enzyme.
胃饥饿素是一种胃肽激素，其中丝氨酸3（青蛙中为苏氨酸3）主要被正辛酸修饰；这种修饰对胃饥饿素的活性至关重要。已鉴定出将正辛酸转移至胃饥饿素肽第三个丝氨酸残基的酶，并将其命名为胃饥饿素O-酰基转移酶（GOAT）。GOAT是唯一已知的催化胃饥饿素酰基修饰的酶，它特异性修饰第三个氨基酸丝氨酸，而不修饰胃饥饿素肽中的其他丝氨酸残基。尽管在胃中，正辛酰形式是主要的酰基修饰胃饥饿素，而正己酰形式的浓度非常低，但GOAT更倾向于以正己酰辅酶A而非正辛酰辅酶A作为酰基供体。此外，源自胃饥饿素N端序列的一个四氨基酸肽可被GOAT修饰，这表明这四个氨基酸构成了该酶识别底物的核心基序。
