5ID9

Crystal structure of equine serum albumin in complex with phosphorodithioate derivative of myristoyl cyclic phosphatidic acid (cPA)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.48 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.173 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties.

Sekula, B.Ciesielska, A.Rytczak, P.Koziokiewicz, M.Bujacz, A.

(2016) Biosci Rep 36

  • DOI: https://doi.org/10.1042/BSR20160089
  • Primary Citation of Related Structures:  
    5ID7, 5ID9

  • PubMed Abstract: 

    Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signalling molecules, which are involved in several pathological states, such as cancer, diabetes or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein-serum albumin. Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids (LPLs). Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer (PC) cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC50 value of 29.0 μM after 24 h incubation, which is almost 30% lower than IC50 of single substituted phosphorothioate cPA. Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this LPL analogue. HSA binds three molecules of Myr-2S-cPA, whereas ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins.


  • Organizational Affiliation

    Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albumin583Equus caballusMutation(s): 0 
UniProt
Find proteins for P35747 (Equus caballus)
Explore P35747 
Go to UniProtKB:  P35747
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35747
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
6A4
Query on 6A4

Download Ideal Coordinates CCD File 
B [auth A](4S)-2-sulfanylidene-4-[(tetradecanoyloxy)methyl]-1,3,2lambda~5~-dioxaphospholane-2-thiolate
C17 H32 O4 P S2
PXJKEDDZAWQNJX-INIZCTEOSA-M
MLI
Query on MLI

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A]
MALONATE ION
C3 H2 O4
OFOBLEOULBTSOW-UHFFFAOYSA-L
FMT
Query on FMT

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
H [auth A],
I [auth A]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.48 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.173 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.86α = 90
b = 93.86β = 90
c = 141.79γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
REFMACphasing
XDSdata reduction
XSCALEdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Polish Ministry of Science and Higher EducationPolandN N405 3639 39
National Science Centre PolandPoland2013/11/B/ST5/02271
National Science Centre PolandPoland2014/12/T/ST5/00136

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-06-15
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description