ALAD porphyria is a conformational disease.

ALAD porphyria is a conformational disease. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

ALAD porphyria is a conformational disease. Abstract Text:

Eileen K Jaffe,Linda Stith,

ALAD porphyria is a rare porphyric disorder, with five documented compound heterozygous patients, and it is caused by a profound lack of porphobilinogen synthase (PBGS) activity. PBGS, also called "delta-aminolevulinate dehydratase," is encoded by the ALAD gene and catalyzes the second step in the biosynthesis of heme. ALAD porphyria is a recessive disorder; there are two common variant ALAD alleles, which encode K59 and N59, and eight known porphyria-associated ALAD mutations, which encode F12L, E89K, C132R, G133R, V153M, R240W, A274T, and V275M. Human PBGS exists as an equilibrium of functionally distinct quaternary structure assemblies, known as "morpheeins," in which one functional homo-oligomer can dissociate, change conformation, and reassociate into a different oligomer. In the case of human PBGS, the two assemblies are a high-activity octamer and a low-activity hexamer. The current study quantifies the morpheein forms of human PBGS for the common and porphyria-associated variants. Heterologous expression in Escherichia coli, followed by separation of the octameric and hexameric assemblies on an ion-exchange column, showed that the percentage of hexamer for F12L (100%), R240W (80%), G133R (48%), C132R (36%), E89K (31%), and A274T (14%) was appreciably larger than for the wild-type proteins K59 and N59 (0% and 3%, respectively). All eight porphyria-associated variants, including V153M and V275M, showed an increased propensity to form the hexamer, according to a kinetic analysis. Thus, all porphyria-associated human PBGS variants are found to shift the morpheein equilibrium for PBGS toward the less active hexamer. We propose that the disequilibrium of morpheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease.

ALAD porphyria is a conformational disease. Publishing Authors By Initials

EK Jaffe,L Stith,

For similar proteins: recombinant proteins research abstracts see: proteins: recombinant proteins research

PUBMED ID PMID:

MEDLINE DATE:

ALAD porphyria is a conformational disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of human genetics

VOLUME: 80

Page Numbers: 329-37

Journal Abbreviation: Am. J. Hum. Genet.

ISSN: 0002-9297

DAY: 21

MONTH: 12

YEAR: 2006

ALAD porphyria is a conformational disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370475

ALAD porphyria is a conformational disease. Keywords Mesh Terms:

KEYWORDS: Recombinant Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: ALAD porphyria is a conformational disease. Information

Substance Name: Porphobilinogen Synthase

Registry Number: EC 4.2.1.24

Grant and Affiliation Information for ALAD porphyria is a conformational disease.

AFFILIATION: Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Eileen.Jaffe@fccc.edu

Country: United States

AGENCY: United States NIEHS

GRANT: ES03654

ACRONYM: ES

MEDLINETA: Am J Hum Genet

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

ALAD porphyria is a conformational disease Related Publications

• ALAD porphyria is a conformational disease.
• Chronic pulmonary disease.
• Couples treatment for interpersonal violence: a review of outcome research literature and current clinical practices.
• Lipid levels in sperm, eggs, and during fertilization in Xenopus laevis.
• Modern management of certain chronic diseases of middle life.
• Slowing the growth of health care costs.
• Taking the LEAD. A CMHC empowers staff to take interest in their agency and the larger community.