2LGR

Solution structure of human protein C6orf130, a putative macro domain


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Orphan Macrodomain Protein (Human C6orf130) Is an O-Acyl-ADP-ribose Deacylase: SOLUTION STRUCTURE AND CATALYTIC PROPERTIES.

Peterson, F.C.Chen, D.Lytle, B.L.Rossi, M.N.Ahel, I.Denu, J.M.Volkman, B.F.

(2011) J Biol Chem 286: 35955-35965

  • DOI: https://doi.org/10.1074/jbc.M111.276238
  • Primary Citation of Related Structures:  
    2L8R, 2LGR

  • PubMed Abstract: 

    Post-translational modification of proteins/histones by lysine acylation has profound effects on the physiological function of modified proteins. Deacylation by NAD(+)-dependent sirtuin reactions yields as a product O-acyl-ADP-ribose, which has been implicated as a signaling molecule in modulating cellular processes. Macrodomain-containing proteins are reported to bind NAD(+)-derived metabolites. Here, we describe the structure and function of an orphan macrodomain protein, human C6orf130. This unique 17-kDa protein is a stand-alone macrodomain protein that occupies a distinct branch in the phylogenic tree. We demonstrate that C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADP-ribose (ADPr) and acetate, propionate, and butyrate, respectively. Using NMR spectroscopy, we solved the structure of C6orf130 in the presence and absence of ADPr. The structures showed a canonical fold with a deep ligand (ADPr)-binding cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex revealed fluctuations of the β(5)-α(4) loop that covers the bound ADPr, suggesting that the β(5)-α(4) loop functions as a gate to sequester substrate and offer flexibility to accommodate alternative substrates. The ADPr-C6orf130 complex identified amino acid residues involved in substrate binding and suggested residues that function in catalysis. Site-specific mutagenesis and steady-state kinetic analyses revealed two critical catalytic residues, Ser-35 and Asp-125. We propose a catalytic mechanism for deacylation of O-acyl-ADP-ribose by C6orf130 and discuss the biological implications in the context of reversible protein acylation at lysine residues.


  • Organizational Affiliation

    Department of Biochemistry and Center for Eukaryotic Structural Genomics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Uncharacterized protein C6orf130160Homo sapiensMutation(s): 0 
Gene Names: BC011709.2C6orf130
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y530 (Homo sapiens)
Explore Q9Y530 
Go to UniProtKB:  Q9Y530
PHAROS:  Q9Y530
GTEx:  ENSG00000124596 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y530
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-08-17
    Type: Initial release
  • Version 1.1: 2011-10-26
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Other