PMID: 8611651Jan 17, 1996Paper

Arginine to tryptophan substitution in the active site of a human lactate dehydrogenase variant--LDHB GUA1: postulated effects on subunit structure and catalysis

Biochimica Et Biophysica Acta
G C ShonnardH W Mohrenweiser

Abstract

A variant of lactate dehydrogenase (LDHB GUA1) was previously identified among the Guaymi Indians of Panama and Costa Rica. The LDHB GUA1 variant is enzymatically inactive; however, the variant subunits alter the electrophoretic mobility of the tetramers that include active LDHA and LDHB subunits. The kinetic properties of the tetrameric enzyme, comprised of the inactive B plus active A subunits, are similar to properties of the heterotetramers with active B subunits, except for the reduced specific activity. We have determined that a single C.G to T.A transition changes an Arg to a Trp at amino acid residue 106. This substitution explains the increase in net negative charge observed by protein electrophoresis. This Arg 106 residue is absolutely conserved throughout evolution. Published high-resolution crystal structures of LDH reveal that this residue is within the hinge of a loop that closes over the active site of the subunit upon binding of substrate and cofactor and also has a direct role in catalysis. Computer modeling of the variant enzyme suggests that replacement of this Arg residue with a Trp does not induce significant change in the structure of the active site. However, this substitution would result in disruption o...Continue Reading

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
May 29, 1991·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C R DunnJ J Holbrook
Nov 1, 1991·PCR Methods and Applications·L Hillier, P Green
Mar 1, 1989·Trends in Biochemical Sciences·A R ClarkeJ J Holbrook
Apr 1, 1989·Trends in Biochemical Sciences·A R ClarkeJ J Holbrook
Feb 1, 1989·The Biochemical Journal·T Takeno, S S Li
Dec 5, 1987·Journal of Molecular Biology·C Abad-ZapateroM G Rossmann
Jun 1, 1982·American Journal of Physical Anthropology·R BarrantesH Gershowitz
Mar 18, 1982·Biochimica Et Biophysica Acta·H W Mohrenweiser, J E Novotny

❮ Previous
Next ❯

Citations

Oct 6, 1999·Clinica Chimica Acta; International Journal of Clinical Chemistry·N OkumuraT Katsuyama
Jul 2, 2015·Journal of Biochemistry·Lulu Ahmed MohamedHideki Nakanishi
Aug 18, 2001·Molecular Genetics and Metabolism·T TakataniY Okamoto

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.