HDC PROTEIN DOMAIN
PROTEIN DOMAIN
Histidine decarboxylase is a highly conserved protein throughout the animal kingdom. It's role in the human body is catalytic and important in many biological cascades.
Protein domains are one of the many building blocks used to categorize proteins. A domain is a structural and functional unit within a protein and plays a role in contributing to a specific function or interaction unique to the protein it resides in [1]. Domains can vary in length and are independently stable.
Protein domains are one of the many building blocks used to categorize proteins. A domain is a structural and functional unit within a protein and plays a role in contributing to a specific function or interaction unique to the protein it resides in [1]. Domains can vary in length and are independently stable.
HDC DOMAIN
One primary protein domain is known to contribute to the unique function of the HDC protein. The Pyridoxal_deC [Pyridoxal-dependent decarboxylase conserved domain] is the functional protein domain found in all variations of HDC and is 378 amino acids in length, on average [2]. This domain is the active form of vitamin B6 and acts as a coenzyme in many reactions including the decarboxylation of histidine as associated with Tourette Syndrome. In Figure 1, you will be able to view the different lengths of each Pyridoxal_deC domain in each organism mentioned thus far.
TOURETTE SYNDROME AND THE HDC PROTEIN DOMAIN
In association with Tourette Syndrome, the Hdc gene has undergone a single point mutation. The location of this mutation is at the amino acid place 317 (W317X), resulting in a product of only 316 amino acids, short 346 amino acids from the wild type (662 amino acids). The mutation is located within the Peridoxal_deC domain on the Hdc gene [2]. After screens of the protein produced from the truncated protein domain were analyzed, no enzymatic activity was noted. The mutation was determined to work in a dominant-negative manner [›]. Without histidine decarboxylase present in the cells, histidine cannot be converted to histamine. This proves that the location and severity of this point mutation within the protein domain is sufficient enough to cause irregular phenotypes, such as those associated with Tourette Syndrome.
|
Header Image Credit http://www.nature.com/nrm/journal/v4/n2/fig_tab/nrm1019_F2.html
REFERENCES
1 "What are protein domains?" EMBL-EBI. Retrieved 23 Feb 2014 http://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
2 "L-Histidine Decarboxylase and Tourette's Syndrome" NIH Public Access: Author Manuscript. Retrieved 24 Mar 2014 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894694/figure/F3/
3 "Histidine Decarboxylase" OMIM Entry. Retrieved 24 Mar 2014 http://omim.org/entry/142704#142704Variants0001
REFERENCES
1 "What are protein domains?" EMBL-EBI. Retrieved 23 Feb 2014 http://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
2 "L-Histidine Decarboxylase and Tourette's Syndrome" NIH Public Access: Author Manuscript. Retrieved 24 Mar 2014 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894694/figure/F3/
3 "Histidine Decarboxylase" OMIM Entry. Retrieved 24 Mar 2014 http://omim.org/entry/142704#142704Variants0001
University of Wisconsin – Madison
Spring 2014 Genetics 564 |
|