Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB.

Protein Science : a Publication of the Protein Society
Karolina MichalskaAndrzej Joachimiak

Abstract

Intracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for l-Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB - a bifunctional enzyme catalyzing the last two steps in l-Trp synthesis. TrpA (subunit α) converts indole-3-glycerol phosphate into indole and glyceraldehyde-3-phosphate (α reaction). The former compound is subsequently used by TrpB (subunit β) to produce l-Trp in the presence of l-Ser and a pyridoxal 5'-phosphate cofactor (β reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yet remains associated with TrpB to support the β reaction. Here, we provide detailed analysis of the TrpAB from C. trachomatis D/UW-3/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four-fold. The side chain of non-conserved βArg267 functions as cation effector, potentially rendering the enzyme less susceptible to the...Continue Reading

References

Dec 1, 1990·The Journal of Infectious Diseases·R B JonesM K Shepard
Nov 1, 1993·The Journal of Infectious Diseases·J T GraystonJ Altman
May 16, 1998·Biochemistry·T R SchneiderI Schlichting
Apr 14, 2000·The Journal of Infectious Diseases·J SomaniC M Black
Jan 5, 2002·The Journal of Biological Chemistry·Michael WeyandAndrea Mozzarelli
Jan 5, 2002·The Journal of Biological Chemistry·Michael WeyandAndrea Mozzarelli
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi Akashi, Takashi Gojobori
May 16, 2002·The Journal of Biological Chemistry·Christine Fehlner-GardinerGrant McClarty
Dec 4, 2002·Journal of Molecular Biology·Victor KulikIlme Schlichting
Jun 5, 2003·The Journal of Clinical Investigation·Harlan D CaldwellGrant McClarty
Jul 2, 2003·Acta Crystallographica. Section D, Biological Crystallography·Jennifer E Padilla, Todd O Yeates
Mar 25, 2004·Infection and Immunity·Richard J HoganPeter Timms
Jun 25, 2004·Nucleic Acids Research·Ian W DavisDavid C Richardson
Sep 29, 2004·Biochemical and Biophysical Research Communications·Mi Suk JeongSe Bok Jang
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 27, 2005·FEMS Microbiology Reviews·Yasser M Abdelrahman, Robert J Belland
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy
Sep 24, 2010·Future Microbiology·Kelsi M Sandoz, Daniel D Rockey
Dec 15, 2010·Journal of the American Chemical Society·Jinfeng LaiLeonard J Mueller
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Sep 13, 2011·Methods : a Companion to Methods in Enzymology·Youngchang KimAndrzej Joachimiak
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Dec 30, 2014·Molecular Biology and Evolution·Joel O WertheimKonrad Scheffler
Nov 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andrew R BullerFrances H Arnold

❮ 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.