Affiliation:
1. Structural Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi – 110067, India
Abstract
:
Serine is ubiquitously synthesized in all living organisms from the glycolysis intermediate
3-phosphoglycerate (PGA) by phosphoserine biosynthetic pathway, consisting of three different
enzymes, namely: 3-phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase
(PSAT), and phosphoserine phosphatase (PSP). Any functional defect or mutation in these
enzymes may cause deliberating conditions, such as colon cancer progression and chemoresistance
in humans. Phosphoserine aminotransferase (PSAT) is the second enzyme in this pathway that converts
phosphohydroxypyruvate (PHP) to O-phospho-L-serine (OPLS).
:
Humans encode two isoforms of this enzyme: PSAT1 and PSAT2. PSAT1 exists as a functional
dimer, where each protomer has a large and a small domain; each large domain contains a Lys residue
that covalently binds PLP. The PLP-binding site of human PSAT1 and most of its active site
residues are highly conserved in all known PSAT structures except for Cys-80. Interestingly, Two
PSAT structures from different organisms show halide binding near their active site. While the human
PSAT1 shows a water molecule at this site with different interacting residues, suggesting the
inability of halide binding in the human enzyme. Analysis of the human PSAT1 structure showed a
big patch of positive charge around the active site, in contrast to the bacterial PSATs. Compared to
human PSAT1, the PSAT2 isoform lacks 46 residues at its C-terminal tail. This tail region is present
at the opening of the active site as observed in the other PSAT structures. Further structural
work on human PSAT2 may reveal the functional importance of these 46 residues.
Publisher
Bentham Science Publishers Ltd.
Subject
Biochemistry,General Medicine,Structural Biology
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献