PDBsum entry 6fd6

Transferase

PDB id: 6fd6

Contents

Protein chains

178 a.a.

Ligands

AMP ×2

PPV ×2

Metals

_MG

Waters ×179

PDB id:

6fd6

Name:

Transferase

Title:

Crystal structure of human aprt-tyr105phe variant in complex with adenine, prpp and mg2+, 30 days post crystallization (with amp and ppi products fully generated)

Structure:

Adenine phosphoribosyltransferase. Chain: a, b. Synonym: aprt. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: aprt. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.153 R-free: 0.183

Authors:

P.Nioche,J.Huyet,M.Ozeir

Key ref:

J.Huyet et al. (2018). Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase. Cell Chem Biol, 25, 666. PubMed id: 29576532 DOI: 10.1016/j.chembiol.2018.02.011

Date:

21-Dec-17 Release date: 15-Aug-18

Protein chains

P07741  (APT_HUMAN) -  Adenine phosphoribosyltransferase from Homo sapiens

Seq: 180 a.a.

Struc: 178 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.4.2.7 - adenine phosphoribosyltransferase.
• Pathway: Ribose activation
• Reaction: AMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + adenine

AMP (Bound ligand (Het Group name = AMP) corresponds exactly) + diphosphate (Bound ligand (Het Group name = PPV) corresponds exactly) = 5-phospho-alpha-D-ribose 1-diphosphate + adenine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.chembiol.2018.02.011

Cell Chem Biol 25:666 (2018)

PubMed id: 29576532

Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase.

J.Huyet, M.Ozeir, M.C.Burgevin, B.Pinson, F.Chesney, J.M.Remy, A.R.Siddiqi, R.Lupoli, G.Pinon, C.Saint-Marc, J.F.Gibert, R.Morales, I.Ceballos-Picot, R.Barouki, B.Daignan-Fornier, A.Olivier-Bandini, F.Augé, P.Nioche.

ABSTRACT

Phosphoribosyltransferases catalyze the displacement of a PRPP α-1'-pyrophosphate to a nitrogen-containing nucleobase. How they control the balance of substrates/products binding and activities is poorly understood. Here, we investigated the human adenine phosphoribosyltransferase (hAPRT) that produces AMP in the purine salvage pathway. We show that a single oxygen atom from the Tyr105 side chain is responsible for selecting the active conformation of the 12 amino acid long catalytic loop. Using in vitro, cellular, and in crystallo approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of the forward and reverse reactions. Together, our results reveal an evolutionary pressure on the strictly conserved Tyr105 and on the dynamic motion of the flexible loop in phosphoribosyltransferases that is essential for purine biosynthesis in cells. These data also provide the framework for designing novel adenine derivatives that could modulate, through hAPRT, diseases-involved cellular pathways.