Cap-domain closure enables diverse substrate recognition by the C2-type haloacid dehalogenase-like sugar phosphatase Plasmodium falciparum HAD1

Acta Crystallographica. Section D, Biological Crystallography
Jooyoung ParkNiraj H Tolia

Abstract

Haloacid dehalogenases (HADs) are a large enzyme superfamily of more than 500,000 members with roles in numerous metabolic pathways. Plasmodium falciparum HAD1 (PfHAD1) is a sugar phosphatase that regulates the methylerythritol phosphate (MEP) pathway for isoprenoid synthesis in malaria parasites. However, the structural determinants for diverse substrate recognition by HADs are unknown. Here, crystal structures were determined of PfHAD1 in complex with three sugar phosphates selected from a panel of diverse substrates that it utilizes. Cap-open and cap-closed conformations are observed, with cap closure facilitating substrate binding and ordering. These structural changes define the role of cap movement within the major subcategory of C2 HAD enzymes. The structures of an HAD bound to multiple substrates identifies binding and specificity-determining residues that define the structural basis for substrate recognition and catalysis within the HAD superfamily. While the substrate-binding region of the cap domain is flexible in the open conformations, this region becomes ordered and makes direct interactions with the substrate in the closed conformations. These studies further inform the structural and biochemical basis for cataly...Continue Reading

References

Jun 11, 1999·Bioscience, Biotechnology, and Biochemistry·T KuzuyamaH Seto
Sep 28, 2002·Nature Structural Biology·Agnes Rinaldo-MatthisPär Nordlund
Nov 7, 2002·Methods in Enzymology·Jean-François ColletEmile Van Schaftingen
Mar 18, 2003·The Journal of Biological Chemistry·Jing Wu, Ronald W Woodard
Oct 14, 2003·The Journal of Biological Chemistry·Youngchang KimDinesh Christendat
Jul 9, 2004·Molecular & Cellular Proteomics : MCP·Andrei AlexandrovElizabeth J Grayhack
Sep 1, 2004·Trends in Biochemical Sciences·Karen N Allen, Debra Dunaway-Mariano
Sep 29, 2004·The Journal of Biological Chemistry·María B CasseraAlejandro M Katzin
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Nov 22, 2005·Biochimica Et Biophysica Acta·Claudio PassarielloGian Maria Rossolini
May 4, 2006·The Journal of Biological Chemistry·Juliette FortpiedEmile Van Schaftingen
Sep 13, 2006·The Journal of Biological Chemistry·Erumbi S RangarajanMiroslaw Cygler
Sep 23, 2006·The Journal of Biological Chemistry·Ekaterina KuznetsovaAlexander F Yakunin
Feb 9, 2007·FEMS Microbiology Letters·Björn TitzPeter Uetz
Sep 4, 2009·The Journal of Biological Chemistry·Tapan BiswasOleg V Tsodikov
Nov 6, 2009·Current Opinion in Structural Biology·Karen N Allen, Debra Dunaway-Mariano
Dec 19, 2009·Molecular and Biochemical Parasitology·Audrey R Odom, Wesley C Van Voorhis
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Jun 22, 2011·The Journal of Experimental Medicine·Sethu C NairBoris Striepen
Nov 19, 2011·Nucleic Acids Research·Sarah HunterSiew-Yit Yong
May 23, 2012·The FEBS Journal·Annegrit SeifriedAntje Gohla
Jul 25, 2014·Nature Communications·Ann M GuggisbergAudrey R Odom
Sep 12, 2014·The Journal of Biological Chemistry·Chetanya PandyaKaren N Allen

❮ Previous
Next ❯

Citations

Jul 3, 2020·Journal of Biomolecular Structure & Dynamics·Javad Zamani AmirzakariaTahmineh Lohrasebi
Jun 18, 2019·Microbiology Insights·Philip M Frasse, Audrey R Odom John

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.