A role for quaternary structure in the substrate specificity of leucine dehydrogenase

Structure
P J BakerD W Rice

Abstract

Glutamate, phenylalanine and leucine dehydrogenases catalyze the NAD(P)(+)-linked oxidative deamination of L-amino acids to the corresponding 2-oxoacids, and sequence homology between these enzymes clearly indicates the existence of an enzyme superfamily related by divergent evolution. We have undertaken structural studies on a number of members of this family in order to investigate the molecular basis of their differential amino acid specificity. We have solved the X-ray structure of the leucine dehydrogenase from Bacillus sphaericus to a resolution of 2.2 A. Each subunit of this octameric enzyme contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle. Comparison of the structure of leucine dehydrogenase with a hexameric glutamate dehydrogenase has shown that these two enzymes share a related fold and possess a similar catalytic chemistry. A mechanism for the basis of the differential amino acid specificity between these enzymes involves point mutations in the amino acid side-chain specificity pocket and subtle changes in the shape of this pocket caused ...Continue Reading

References

Dec 1, 1991·Journal of Molecular Graphics·C C HuangR Langridge
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Dec 5, 1987·Journal of Molecular Biology·C Abad-ZapateroM G Rossmann
Jan 1, 1985·Methods in Enzymology·R Hamlin
Jan 1, 1985·Methods in Enzymology·A J HowardN H Xuong
Jul 19, 1974·Nature·M G RossmannK W Olsen
Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Aug 1, 1980·Quarterly Reviews of Biophysics·C I Brändeén
May 27, 1980·Biochemistry·J E Rife, W W Cleland
Sep 1, 1961·Archives of Biochemistry and Biophysics·B D SANWAL, M W ZINK
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·K Y Zhang

❮ Previous
Next ❯

Citations

Jun 1, 1997·Proteins·A V Efimov
Nov 29, 2011·Applied Microbiology and Biotechnology·Yinxia LiYoshihiro Sawa
Sep 18, 1997·Trends in Neurosciences·G Oliver, P Gruss
Aug 18, 1999·Bioorganic & Medicinal Chemistry Letters·A Sutherland, C L Willis
May 6, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Sarvind Mani Tripathi, Ravishankar Ramachandran
Sep 5, 2009·PLoS Computational Biology·Julie Baussand, Alessandra Carbone
Oct 28, 2014·Chemical Communications : Chem Comm·Bettina R BommariusAndreas S Bommarius
Feb 24, 2016·Applied Microbiology and Biotechnology·Lin ZhuShuang-Yan Tang
Oct 19, 2016·Biotechnology and Applied Biochemistry·Alexandra LerchnerArne Skerra
Mar 8, 2012·Angewandte Chemie·Michael J AbrahamsonAndreas S Bommarius
Jul 9, 1999·Archives of Biochemistry and Biophysics·F Fan, B V Plapp
Nov 7, 2016·Applied and Environmental Microbiology·Taisuke WakamatsuToshihisa Ohshima
Jan 25, 2018·Chemical Society Reviews·Ya-Ping XueYu-Guo Zheng
Dec 22, 2016·Applied Biochemistry and Biotechnology·Jian-Miao XuYu-Guo Zheng
Mar 23, 2011·Neurochemistry International·Paul C Engel

❮ 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.