Crystal Structure of Histidine Ammonia-Lyase Revealing a Novel Polypeptide Modification as the Catalytic Electrophile,
- 1 April 1999
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 38 (17) , 5355-5361
- https://doi.org/10.1021/bi982929q
Abstract
Histidine ammonia-lyase (EC 4.3.1.3) catalyzes the nonoxidative elimination of the α-amino group of histidine and is closely related to the important plant enzyme phenylalanine ammonia-lyase. The crystal structure of histidase from Pseudomonas putida was determined at 2.1 Å resolution revealing a homotetramer with D2 symmetry, the molecular center of which is formed by 20 nearly parallel α-helices. The chain fold, but not the sequence, resembles those of fumarase C and related proteins. The structure shows that the reactive electrophile is a 4-methylidene-imidazole-5-one, which is formed autocatalytically by cyclization and dehydration of residues 142−144 with the sequence Ala-Ser-Gly. With respect to the first dehydration step, this modification resembles the chromophore of the green fluorescent protein. The active center is clearly established by the modification and by mutations. The observed geometry allowed us to model the bound substrate at a high confidence level. A reaction mechanism is proposed.Keywords
This publication has 16 references indexed in Scilit:
- Locating proper non-crystallographic symmetry in low-resolution electron-density maps with the programGETAXActa Crystallographica Section D-Biological Crystallography, 1999
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa Crystallographica Section D-Biological Crystallography, 1997
- Phase combination and cross validation in iterated density-modification calculationsActa Crystallographica Section D-Biological Crystallography, 1996
- AMoRe: an automated package for molecular replacementActa Crystallographica Section A Foundations of Crystallography, 1994
- Protein Structure Comparison by Alignment of Distance MatricesJournal of Molecular Biology, 1993
- PROCHECK: a program to check the stereochemical quality of protein structuresJournal of Applied Crystallography, 1993
- The application of direct methods and Patterson interpretation to high-resolution native protein dataActa Crystallographica Section D-Biological Crystallography, 1993
- Automated refinement of protein modelsActa Crystallographica Section D-Biological Crystallography, 1993
- MOLSCRIPT: a program to produce both detailed and schematic plots of protein structuresJournal of Applied Crystallography, 1991
- Physiology and Molecular Biology of Phenylpropanoid MetabolismAnnual Review of Plant Biology, 1989