Structures of two histidine ammonia-lyase modifications and implications for the catalytic mechanism.
Eur J Biochem
; 269(6): 1790-7, 2002 Mar.
Article
en En
| MEDLINE
| ID: mdl-11895450
Histidine ammonia-lyase (EC 4.3.1.3) catalyzes the nonoxidative elimination of the alpha-amino group of histidine using a 4-methylidene-imidazole-5-one (MIO), which is formed autocatalytically from the internal peptide segment 142Ala-Ser-Gly. The structure of the enzyme inhibited by a reaction with l-cysteine was established at the very high resolution of 1.0 A. Five active center mutants were produced and their catalytic activities were measured. Among them, mutant Tyr280-->Phe could be crystallized and its structure could be determined at 1.7 A resolution. It contains a planar sp2-hybridized 144-N atom of MIO, in contrast to the pyramidal sp3-hybridized 144-N of the wild-type. With the planar 144-N atom, MIO assumes the conformation of a putative intermediate aromatic state of the reaction, demonstrating that the conformational barrier between aromatic and wild-type states is very low. The data led to a new proposal for the geometry for the catalyzed reaction, which also applies to the closely related phenylalanine ammonia-lyase (EC 4.3.1.5). Moreover, it suggested an intermediate binding site for the released ammonia.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histidina Amoníaco-Liasa
Idioma:
En
Revista:
Eur J Biochem
Año:
2002
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido