Glutaminyl cyclases display significant catalytic proficiency for glutamyl substrates.

Abstract:

:N-Terminal glutaminyl and glutamyl residues of peptides and proteins tend to form pyroglutamic acid (pGlu) by intramolecular cylization. The rate constants for spontaneous cyclization of glutamine (10(-6) s(-1)) and glutamic acid (10(-9) s(-1)) in aqueous solution differ by approximately 3 orders of magnitude at pH 6.5. Glutaminyl cyclases (QCs) from plants and mammals accelerate pGlu formation. Human QC exhibits a rate enhancement of 2.2 x 10(5) for glutamate cyclization, approximately 2 orders of magnitude lower than that of the corresponding N-terminal glutaminyl reaction. Thus, glutaminyl cyclases are enzymes with only modest specificity for cyclization of their primary glutaminyl substrates and may provide a link between glutamate cyclization and pathophysiology.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Seifert F,Schulz K,Koch B,Manhart S,Demuth HU,Schilling S

doi

10.1021/bi9018835

subject

Has Abstract

pub_date

2009-12-22 00:00:00

pages

11831-3

issue

50

eissn

0006-2960

issn

1520-4995

journal_volume

48

pub_type

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