Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop

Maria A. Schumacher, Darrick Carter, David S. Roos, Buddy Ullman, Richard G. Brennan

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Crystal structures of substrate-free and XMP-soaked hypoxanthine- guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 Å resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115-126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.

Original languageEnglish (US)
Pages (from-to)881-887
Number of pages7
JournalNature Structural Biology
Volume3
Issue number10
DOIs
StatePublished - Oct 1996

Fingerprint

Toxoplasma
Catalytic Domain
Crystal structure
Relocation
Dipeptides
Pathogens
Substrates
Enzymes
hypoxanthine-guanine-xanthine phosphoribosyltransferase
xanthosine monophosphate

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop. / Schumacher, Maria A.; Carter, Darrick; Roos, David S.; Ullman, Buddy; Brennan, Richard G.

In: Nature Structural Biology, Vol. 3, No. 10, 10.1996, p. 881-887.

Research output: Contribution to journalArticle

Schumacher, Maria A. ; Carter, Darrick ; Roos, David S. ; Ullman, Buddy ; Brennan, Richard G. / Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop. In: Nature Structural Biology. 1996 ; Vol. 3, No. 10. pp. 881-887.
@article{b6850de95fee44a99b367a05c9c9ae7e,
title = "Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop",
abstract = "Crystal structures of substrate-free and XMP-soaked hypoxanthine- guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 {\AA} resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115-126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.",
author = "Schumacher, {Maria A.} and Darrick Carter and Roos, {David S.} and Buddy Ullman and Brennan, {Richard G.}",
year = "1996",
month = "10",
doi = "10.1038/nsb1096-881",
language = "English (US)",
volume = "3",
pages = "881--887",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop

AU - Schumacher, Maria A.

AU - Carter, Darrick

AU - Roos, David S.

AU - Ullman, Buddy

AU - Brennan, Richard G.

PY - 1996/10

Y1 - 1996/10

N2 - Crystal structures of substrate-free and XMP-soaked hypoxanthine- guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 Å resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115-126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.

AB - Crystal structures of substrate-free and XMP-soaked hypoxanthine- guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 Å resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115-126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.

UR - http://www.scopus.com/inward/record.url?scp=0029742013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029742013&partnerID=8YFLogxK

U2 - 10.1038/nsb1096-881

DO - 10.1038/nsb1096-881

M3 - Article

C2 - 8836106

AN - SCOPUS:0029742013

VL - 3

SP - 881

EP - 887

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 10

ER -