PDBsum entry 2bfq

Adp ribose-binding protein

PDB id: 2bfq

Contents

Protein chain

192 a.a. *

Ligands

AR6

Waters ×155

* Residue conservation analysis

PDB id:

2bfq

Name:

Adp ribose-binding protein

Title:

Macro domains are adp-ribose binding molecules

Structure:

Hypothetical protein af1521. Chain: a. Engineered: yes

Source:

Archaeoglobus fulgidus. Organism_taxid: 2234. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: c41.

Resolution:

1.50Å R-factor: 0.210 R-free: 0.233

Authors:

G.I.Karras,H.R.Buhecha,M.D.Allen,C.Pugieux,F.Sait,M.Bycroft, A.G.Ladurner

Key ref:

G.I.Karras et al. (2005). The macro domain is an ADP-ribose binding module. EMBO J, 24, 1911-1920. PubMed id: 15902274 DOI: 10.1038/sj.emboj.7600664

Date:

10-Dec-04 Release date: 18-Jan-05

Protein chain

O28751  (Y1521_ARCFU) -  ADP-ribose glycohydrolase AF_1521 from Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16)

Seq: 192 a.a.

Struc: 192 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.2.2.- - ?????

DOI no: 10.1038/sj.emboj.7600664

EMBO J 24:1911-1920 (2005)

PubMed id: 15902274

The macro domain is an ADP-ribose binding module.

G.I.Karras, G.Kustatscher, H.R.Buhecha, M.D.Allen, C.Pugieux, F.Sait, M.Bycroft, A.G.Ladurner.

ABSTRACT

The ADP-ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, transcription, chromatin biology and long-term memory formation. Yet no protein modules are known that specifically recognize the ADP-ribose nucleotide. We provide biochemical and structural evidence that macro domains are high-affinity ADP-ribose binding modules. Our structural analysis reveals a conserved ligand binding pocket among the macro domain fold. Consistently, distinct human macro domains retain their ability to bind ADP-ribose. In addition, some macro domain proteins also recognize poly-ADP-ribose as a ligand. Our data suggest an important role for proteins containing macro domains in the biology of ADP-ribose.

Selected figure(s)

Figure 4.
Figure 4 Structure of the complex formed between Af1521 and ADP-ribose. (A) The ADP-ribose molecule binds the Af1521 macro domain in an L-shaped cleft. The ADP-ribose ligand is shown as a ball-and-stick model. (B) Structure of the complex between Af1521 and ADP. The structure is highly similar to that of the complex between Af1521 and ADP-ribose, but a number of interactions that contribute to ADP-ribose specificity and affinity cannot occur. The ADP ligand is shown as a ball-and-stick model.

Figure 5.
Figure 5 Specificity of the macro domain fold for ADP-ribose. (A) Electron density for the ADP-ribose ligand in the pocket of the Af1521 protein. The ADP-ribose ligand is shown as a ball-and-stick model. (B) Stereo-diagram of the ADP-ribose binding pocket. A number of critical interactions between the ligand and the Af1521 macro domain are shown. Several of the interactions involve hydrogen bonds between side chains (Asn 34, Asp 20) and backbone amide bonds. Specific aromatic stacking interactions occur between Tyr 176 and the adenine base. The phosphates are stabilized by a number of interactions, including the backbone amide of Val 43, Ser 141 and the favorable dipole of helix 1. (C) Schematic representation for the binding of ADP-ribose to the macro domain. The LigPlot (Wallace et al, 1995) diagram summarizes key noncovalent interactions between the ADP-ribose ligand and the Af1521 macro domain. Legend: thick blue lines, ADP-ribose ligand; thin red lines, macro domain residues; circles or semicircles with radiating lines; atoms or residues involved in hydrophobic contacts between protein and ligand.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2005, 24, 1911-1920) copyright 2005.

Figures were selected by an automated process.