|
type |
Journal Article |
authors |
Komori H, Nitta Y, Ueno H, Higuchi Y. |
title |
Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase. |
journal |
J Biol Chem. |
Activity |
4.1.1.22 |
Family |
4.1.1.22.b |
sel |
unselected |
ui |
22767596 |
year |
(2012) |
volume |
287 |
number |
34 |
pages |
29175-83 |
| |
abstract |
Histamine is an important chemical mediator for a wide variety of physiological reactions. L-histidine decarboxylase (HDC) is the primary enzyme responsible for histamine synthesis and produces histamine from histidine in a one-step reaction. In this study, we determined the crystal structure of human HDC (hHDC) complexed with the inhibitor histidine methyl ester. This structure shows the detailed features of the pyridoxal-5'-phosphate inhibitor adduct (external aldimine) at the active site of HDC. Moreover, a comparison of the structures of hHDC and aromatic L-amino acid (L-DOPA) decarboxylase showed that Ser-354 was a key residue for substrate specificity. The S354G mutation at the active site enlarged the size of the hHDC substrate-binding pocket and resulted in a decreased affinity for histidine, but an acquired ability to bind and act on L-DOPA as a substrate. These data provide insight into the molecular basis of substrate recognition among the group II pyridoxal-5'-phosphate-dependent decarboxylases. |
last changed |
2014/03/20 11:44 |
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