Nat Struct Biol. 1999 Jun;6(6):588-93.

The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.

Shi W, Li CM, Tyler PC, Furneaux RH, Grubmeyer C, Schramm VL, Almo SC.

Source

Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Abstract

The structure of human HGPRT bound to the transition-state analog immucillinGP and Mg2+-pyrophosphate has been determined to 2.0 A resolution. ImmucillinGP was designed as a stable analog with the stereoelectronic features of the transition state. Bound inhibitor at the catalytic site indicates that the oxocarbenium ion of the transition state is stabilized by neighboring-group participation from MgPPi and O5'. A short hydrogen bond forms between Asp 137 and the purine ring analog. Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls of the ribosyl analog. The transition-state analog is shielded from bulk solvent by a catalytic loop that moves approximately 25 A to cover the active site and becomes an ordered antiparallel beta-sheet.

Comment in

Nat Struct Biol. 1999 Jun;6(6):502-4.

PMID:: 10360366; [PubMed - indexed for MEDLINE]

MeSH Terms, Substances, Secondary Source ID

MeSH Terms

Substances

Secondary Source ID

PDB/1BZY

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Medical

HPRT1 Gene - Genetics Home Reference

Molecular Biology Databases

Supplemental Content

Save items

Related citations in PubMed

A transition-state analogue reduces protein dynamics in hypoxanthine-guanine phosphoribosyltransferase. [Biochemistry. 2001]
A transition-state analogue reduces protein dynamics in hypoxanthine-guanine phosphoribosyltransferase.
Wang F, Shi W, Nieves E, Angeletti RH, Schramm VL, Grubmeyer C. Biochemistry. 2001 Jul 10; 40(27):8043-54.
The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor. [Biochemistry. 1999]
The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor.
Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC. Biochemistry. 1999 Aug 3; 38(31):9872-80.
Crystal structures of Giardia lamblia guanine phosphoribosyltransferase at 1.75 A(,). [Biochemistry. 2000]
Crystal structures of Giardia lamblia guanine phosphoribosyltransferase at 1.75 A(,).
Shi W, Munagala NR, Wang CC, Li CM, Tyler PC, Furneaux RH, Grubmeyer C, Schramm VL, Almo SC. Biochemistry. 2000 Jun 13; 39(23):6781-90.
Transition-state analogs as inhibitors of human and malarial hypoxanthine-guanine phosphoribosyltransferases. [Nat Struct Biol. 1999]
Transition-state analogs as inhibitors of human and malarial hypoxanthine-guanine phosphoribosyltransferases.
Li CM, Tyler PC, Furneaux RH, Kicska G, Xu Y, Grubmeyer C, Girvin ME, Schramm VL. Nat Struct Biol. 1999 Jun; 6(6):582-7.
Review Enzymatic transition states: thermodynamics, dynamics and analogue design. [Arch Biochem Biophys. 2005]
Review Enzymatic transition states: thermodynamics, dynamics and analogue design.
Schramm VL. Arch Biochem Biophys. 2005 Jan 1; 433(1):13-26.

See reviews... See all...

Cited by 11 PubMed Central articles

Review Purine and pyrimidine pathways as targets in Plasmodium falciparum. [Curr Top Med Chem. 2011]
Review Purine and pyrimidine pathways as targets in Plasmodium falciparum.
Cassera MB, Zhang Y, Hazleton KZ, Schramm VL. Curr Top Med Chem. 2011; 11(16):2103-15.
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT. [Proc Natl Acad Sci U S A. 2009]
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT.
Burgos ES, Ho MC, Almo SC, Schramm VL. Proc Natl Acad Sci U S A. 2009 Aug 18; 106(33):13748-53. Epub 2009 Aug 4.
Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase. [Arthritis Rheum. 2009]
Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase.
Ea HK, Bardin T, Jinnah HA, Aral B, Lioté F, Ceballos-Picot I. Arthritis Rheum. 2009 Jul; 60(7):2201-4.

See all...

Structures reported by this article

Human Hgprtase With Transition State Inhibitor

PDB: 1BZY

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2 Å

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioSystems
Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Structure
Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in c...
The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.
Nat Struct Biol. 1999 Jun ;6(6):588-93.

PubMed
Diet and the risk of breast cancer in a case-control study: does the threat of d...
Diet and the risk of breast cancer in a case-control study: does the threat of disease have an influence on recall bias?
J Clin Epidemiol. 1999 May ;52(5):429-39.

PubMed
The potential clinical utility of serum alpha-protryptase levels.
The potential clinical utility of serum alpha-protryptase levels.
J Allergy Clin Immunol. 1999 Jun ;103(6):1092-9.

PubMed
Food allergy. Part 2: diagnosis and management.
Food allergy. Part 2: diagnosis and management.
J Allergy Clin Immunol. 1999 Jun ;103(6):981-9.

PubMed
Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 a...
Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation.
Proc Natl Acad Sci U S A. 1999 Jun 8 ;96(12):6757-62.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: