The X-ray structure of N-methyltryptophan oxidase reveals the structural determinants of substrate specificity

Proteins
Andrea IlariGianni Colotti

Abstract

The X-ray structure of monomeric N-methyltryptophan oxidase from Escherichia coli (MTOX) has been solved at 3.2 A resolution by molecular replacement methods using Bacillus sp. sarcosine oxidase structure (MSOX, 43% sequence identity) as search model. The analysis of the substrate binding site highlights the structural determinants that favour the accommodation of the bulky N-methyltryptophan residue in MTOX. In fact, although the nature and geometry of the catalytic residues within the first contact shell of the FAD moiety appear to be virtually superposable in MTOX and MSOX, the presence of a Thr residue in position 239 in MTOX (Met245 in MSOX) located at the entrance of the active site appears to play a key role for the recognition of the amino acid substrate side chain. Accordingly, a 15 fold increase in k(cat) and 100 fold decrease in K(m) for sarcosine as substrate has been achieved in MTOX upon T239M mutation, with a concomitant three-fold decrease in activity towards N-methyltryptophan. These data provide clear evidence for the presence of a catalytic core, common to the members of the methylaminoacid oxidase subfamily, and of a side chain recognition pocket, located at the entrance of the active site, that can be adjus...Continue Reading

References

Dec 1, 1985·Archives of Biochemistry and Biophysics·D H PorterC Wagner
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P MothetS H Snyder
Jun 1, 1956·Archives of Biochemistry and Biophysics·T P SINGERE B KEARNEY
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 23, 2005·Biochemistry·Erik C Ralph, Paul F Fitzpatrick
Apr 18, 2006·FEBS Letters·Gianluca MollaLoredano Polegioni
Jul 6, 2006·Journal of Molecular Biology·Zhi-wei ChenF Scott Mathews
Aug 2, 2006·Biochemistry·Alshaimaa Hassan-AbdallahMarilyn Schuman Jorns

❮ Previous
Next ❯

Citations

May 21, 2011·BMC Genomics·Bo ZhuGu-Lei Jin
Aug 5, 2009·Archives of Biochemistry and Biophysics·Paul F Fitzpatrick
May 15, 2009·The FEBS Journal·Dominic P H M HeutsMarco W Fraaije
Jul 26, 2014·The FEBS Journal·Malgorzata M KopaczMarco W Fraaije
Nov 5, 2016·Chemical Communications : Chem Comm·Adrian Romero-RiveraSílvia Osuna
Sep 9, 2018·The Journal of Biological Chemistry·Majd LahhamPeter Macheroux
Apr 5, 2021·Archives of Biochemistry and Biophysics·Majd LahhamSilvia Wallner

❮ 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.