UMMS Affiliation

Department of Medicine

Date

2-14-2004

Document Type

Article

Subjects

Amino Acid Sequence; Amino Acids; Animals; Binding Sites; Catalysis; Computational Biology; Cysteine; Histidine Decarboxylase; Molecular Sequence Data; Mutagenesis, Site-Directed; Rats; Sequence Homology, Amino Acid; Swine; Trypsin; Tyrosine

Disciplines

Computational Biology | Genetics and Genomics | Molecular Genetics

Abstract

HDC (L-histidine decarboxylase), the enzyme responsible for the catalytic production of histamine from L-histidine, belongs to an evolutionarily conserved family of vitamin B6-dependent enzymes known as the group II decarboxylases. Yet despite the obvious importance of histamine, mammalian HDC enzymes remain poorly characterized at both the biochemical and structural levels. By comparison with the recently described crystal structure of the homologous enzyme L-DOPA decarboxylase, we have been able to identify a number of conserved domains and motifs that are important also for HDC catalysis. This includes residues that were proposed to mediate events within the active site, and HDC proteins carrying mutations in these residues were inactive when expressed in reticulocyte cell lysates reactions. Our studies also suggest that a significant change in quartenary structure occurs during catalysis. This involves a protease sensitive loop, and incubating recombinant HDC with an L-histidine substrate analogue altered enzyme structure so that the loop was no longer exposed for tryptic proteolysis. In total, 27 mutant proteins were used to test the proposed importance of 34 different amino acid residues. This is the most extensive mutagenesis study yet to identify catalytically important residues in a mammalian HDC protein sequence and it provides a number of novel insights into the mechanism of histamine biosynthesis.

Rights and Permissions

Citation: Biochem J. 2004 Apr 15;379(Pt 2):253-61. Link to article on publisher's site

DOI of Published Version

10.1042/BJ20031525

Related Resources

Link to article in PubMed

Journal Title

The Biochemical journal

PubMed ID

14961766

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.