Active site and loop 4 movements within human glycolate oxidase: implications for substrate specificity and drug design.

Biochemistry
Michael S MurrayW Todd Lowther

Abstract

Human glycolate oxidase (GO) catalyzes the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate, a key metabolite in kidney stone formation. We report herein the structures of recombinant GO complexed with sulfate, glyoxylate, and an inhibitor, 4-carboxy-5-dodecylsulfanyl-1,2,3-triazole (CDST), determined by X-ray crystallography. In contrast to most alpha-hydroxy acid oxidases including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. The lack of electron density for this loop in the GO-CDST complex, which mimics a large substrate, suggests that a disordered to ordered transition may occur with the binding of substrates. The conformational flexibility of Trp110 appears to be responsible for enabling GO to react with alpha-hydroxy acids of various chain lengths. Moreover, the movement of Trp110 disrupts a hydrogen-bonding network between Trp110, Leu191, Tyr134, and Tyr208. This loss of interactions is the first indication that active site movements are directly linked to changes in the conformation of loop 4. The kinetic parameters for the oxidation of glycolate, glyoxylate, and 2-hydroxy octanoate indicate that the oxidatio...Continue Reading

References

Apr 20, 1990·Journal of Molecular Biology·Z X Xia, F S Mathews
Apr 15, 1989·European Journal of Biochemistry·S Ghisla, V Massey
Sep 5, 1989·Journal of Molecular Biology·Y Lindqvist
Dec 15, 1988·European Journal of Biochemistry·G A ReidS K Chapman
Nov 1, 1969·European Journal of Biochemistry·R J Duncan, K F Tipton
Mar 10, 1971·Biochimica Et Biophysica Acta·M Schuman, V Massey
Mar 10, 1971·Biochimica Et Biophysica Acta·M Schuman, V Massey
Feb 1, 1968·The New England Journal of Medicine·H E Williams, L H Smith
Nov 1, 1981·European Journal of Biochemistry·R Ghrir, F Lederer
May 1, 1993·European Journal of Biochemistry·P MacherouxY Lindqvist
May 1, 1997·Protein Science : a Publication of the Protein Society·K Stenberg, Y Lindqvist
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Oct 26, 1999·Acta Crystallographica. Section D, Biological Crystallography·J W Pflugrath
Mar 1, 2000·Trends in Biochemical Sciences·M W Fraaije, A Mattevi
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·W T LowtherB W Matthews
Mar 3, 2004·Acta Crystallographica. Section D, Biological Crystallography·Laurent C StoroniRandy J Read
Jun 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Robert SchwarzenbacherLukasz Jaroszewski
Jun 29, 2004·Urological Research·Ross P Holmes, Dean G Assimos
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 3, 2005·Biochemistry·Louise M CunaneF Scott Mathews
Apr 5, 2005·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoyRandy J Read
Jun 18, 2005·American Journal of Nephrology·Christopher J Danpure
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
Apr 8, 2006·Trends in Biochemical Sciences·Andrea Mattevi
Jun 8, 2006·Annual Review of Biochemistry·Ronald J A Wanders, Hans R Waterham
Sep 30, 2006·Biochemical and Biophysical Research Communications·Yasufumi UmenaYukio Morimoto
Aug 3, 2007·Archives of Biochemistry and Biophysics·Caroline VignaudFlorence Lederer

❮ Previous
Next ❯

Citations

Apr 20, 2011·European Biophysics Journal : EBJ·Florence Lederer
Oct 18, 2011·Journal of the American Chemical Society·Hongling YuanGiovanni Gadda
Sep 18, 2009·The Journal of Biological Chemistry·Andrea Pennati, Giovanni Gadda
Jan 8, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Jean Marie BourhisYlva Lindqvist
Dec 31, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Juquan JiangW Todd Lowther
Jun 3, 2014·BMC Medical Genetics·Nanyawan RungrojPa-Thai Yenchitsomanus
Dec 23, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cristina Martin-HiguerasEduardo Salido
Sep 25, 2012·Critical Care Clinics·James A Kruse
Feb 19, 2010·Urology·Iwao YoshiokaAkihiko Okuyama
Oct 3, 2015·Biochimica Et Biophysica Acta·Xingsheng LiRoss P Holmes
Mar 27, 2012·Biochimica Et Biophysica Acta·Eduardo SalidoVictor Lorenzo
Jul 6, 2014·Journal of Medical Genetics·Yaacov FrishbergRuth Belostotsky
Sep 13, 2018·Protein Science : a Publication of the Protein Society·Kelsey M Kean, P Andrew Karplus
Jul 20, 2016·Journal of the American Society of Nephrology : JASN·Abigail LiebowJohn Knight
Nov 6, 2014·Biomolecular Concepts·Elvira Romero, Giovanni Gadda
Jul 29, 2017·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Oliver Clifford-MobleySenthil Senniappan
Aug 3, 2019·Acta Crystallographica. Section D, Structural Biology·Hsien Wei YehTsung Lin Li
Jul 30, 2019·Archives of Biochemistry and Biophysics·Dan SuGiovanni Gadda
Jan 31, 2021·Journal of Personalized Medicine·Maria Dolores Moya-GarzonMonica Diaz-Gavilan
Jan 29, 2021·Frontiers in Cell and Developmental Biology·Serhii ChornyiHans R Waterham
Jul 17, 2021·ACS Medicinal Chemistry Letters·Jinyue DingDavid A Powell
Jul 22, 2018·Journal of Medicinal Chemistry·María Dolores Moya-GarzónMónica Díaz-Gavilán

❮ 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.

Related Papers

Archives of Biochemistry and Biophysics
Caroline VignaudF Lederer
Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Ingar LeirosEdward Hough
Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Jean Marie BourhisY Lindqvist
© 2021 Meta ULC. All rights reserved