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Probing the active site of rat porphobilinogen synthase using newly developed inhibitors.

Abstract：

:The structurally related tetrapyrrolic pigments are a group of natural products that participate in many of the fundamental biosynthetic and catabolic processes of living organisms. Porphobilinogen synthase catalyzes a rate-limiting step for the biosyntheses of tetrapyrrolic natural products. In the present study, a variety of new substrate analogs and reaction intermediate analogs were synthesized, which were used as probes for studying the active site of rat porphobilinogen synthase. The compounds 1, 3, 6, 9, 14, 16, and 28 were found to be competitive inhibitors of rat porphobilinogen synthase with inhibition constants ranging from 0.96 to 73.04mM. Compounds 7, 10, 12, 13, 15, 17, 18, and 26 were found to be irreversible enzyme inhibitors. For irreversible inhibitors, loose-binding inhibitors were found to give stronger inactivation. The amino group and carboxyl group of the analogs were found to be important for their binding to the enzyme. This study increased our understanding of the active site of porphobilinogen synthase.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Li N,Chu X,Liu X,Li D

doi

10.1016/j.bioorg.2008.11.001

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

33-40

issue

1

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(08)00083-7

journal_volume

37

pub_type

杂志文章

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