6PKF

Myocilin OLF mutant N428E/D478K


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.484 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.150 

wwPDB Validation 3D Report Full Report


This is version 1.2 of the entry. See complete history

Literature

Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices.

Hill, S.E.Cho, H.Raut, P.Lieberman, R.L.

(2019) Acta Crystallogr D Struct Biol 75: 817-824

  • DOI: 10.1107/S205979831901074X
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • Olfactomedins are a family of modular proteins found in multicellular organisms that all contain five-bladed β-propeller olfactomedin (OLF) domains. In support of differential functions for the OLF propeller, the available crystal structures reveal t ...

    Olfactomedins are a family of modular proteins found in multicellular organisms that all contain five-bladed β-propeller olfactomedin (OLF) domains. In support of differential functions for the OLF propeller, the available crystal structures reveal that only some OLF domains harbor an internal calcium-binding site with ligands derived from a triad of residues. For the myocilin OLF domain (myoc-OLF), ablation of the ion-binding site (triad Asp, Asn, Asp) by altering the coordinating residues affects the stability and overall structure, in one case leading to misfolding and glaucoma. Bioinformatics analysis reveals a variety of triads with possible ion-binding characteristics lurking in OLF domains in invertebrate chordates such as Arthropoda (Asp-Glu-Ser), Nematoda (Asp-Asp-His) and Echinodermata (Asp-Glu-Lys). To test ion binding and to extend the observed connection between ion binding and distal structural rearrangements, consensus triads from these phyla were installed in the myoc-OLF. All three protein variants exhibit wild-type-like or better stability, but their calcium-binding properties differ, concomitant with new structural deviations from wild-type myoc-OLF. Taken together, the results indicate that calcium binding is not intrinsically destabilizing to myoc-OLF or required to observe a well ordered side helix, and that ion binding is a differential feature that may underlie the largely elusive biological function of OLF propellers.


    Organizational Affiliation

    School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive NW, Atlanta, GA 30332-0400, USA.,School of Biological Sciences, Georgia Institute of Technology, 310 Ferst Drive NW, Atlanta, GA 30318, USA.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Myocilin
A
277Homo sapiensMutation(s): 2 
Gene Names: MYOC (GLC1A, TIGR)
Find proteins for Q99972 (Homo sapiens)
Go to Gene View: MYOC
Go to UniProtKB:  Q99972
Small Molecules
Ligands 1 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download SDF File 
Download CCD File 
A
GLYCEROL
GLYCERIN; PROPANE-1,2,3-TRIOL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.484 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.150 
  • Space Group: P 21 21 21
Unit Cell:
Length (Å)Angle (°)
a = 45.506α = 90.00
b = 58.688β = 90.00
c = 89.505γ = 90.00
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
PHASERphasing
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Eye Institute (NIH/NEI)United StatesR01EY021205

Revision History 

  • Version 1.0: 2019-09-11
    Type: Initial release
  • Version 1.1: 2019-11-13
    Type: Database references
  • Version 1.2: 2019-12-11
    Type: Author supporting evidence