The reaction mechanism of the internal thioester in the human complement component C4.

Abstract:

:A key step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces. Proteolytic activation of these proteins results in a conformational change, and an internal thioester is exposed which reacts with amino or hydroxyl groups on the target surface to form amide or ester bonds, or is hydrolysed. We report here that the binding of the human C4A isotype involves a direct reaction between amino-nucleophiles and the thioester. A two-step mechanism is used by the C4B isotype. The histidine at position 1,106(aspartic acid in C4A) first attacks the thioester to form an acyl-imidazole intermediate. The released thiol then acts as a base to catalyse the transfer of the acyl group to amino- and hydroxyl-nucleophiles, including water.

journal_name

Nature

journal_title

Nature

authors

Dodds AW,Ren XD,Willis AC,Law SK

doi

10.1038/379177a0

subject

Has Abstract

pub_date

1996-01-11 00:00:00

pages

177-9

issue

6561

eissn

0028-0836

issn

1476-4687

journal_volume

379

pub_type

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