3B9L

Human serum albumin complexed with myristate and AZT


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.223 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography

Zhu, L.Yang, F.Chen, L.Meehan, E.J.Huang, M.

(2008) J Struct Biol 162: 40-49

  • DOI: https://doi.org/10.1016/j.jsb.2007.12.004
  • Primary Citation of Related Structures:  
    3B9L, 3B9M

  • PubMed Abstract: 

    3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA.


  • Organizational Affiliation

    State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, The Chinese Academy of Sciences, 155 Yang Qiao Xi Lu, Fuzhou, Fujian 350002, China. zhulili@fjirsm.ac.cn


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albumin585Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P02768 (Homo sapiens)
Explore P02768 
Go to UniProtKB:  P02768
PHAROS:  P02768
GTEx:  ENSG00000163631 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02768
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AZZ
Query on AZZ

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A]
3'-azido-3'-deoxythymidine
C10 H13 N5 O4
HBOMLICNUCNMMY-XLPZGREQSA-N
MYR
Query on MYR

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A]
MYRISTIC ACID
C14 H28 O2
TUNFSRHWOTWDNC-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AZZ BindingDB:  3B9L Kd: 0.44 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.223 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 183.9α = 90
b = 38.696β = 104.35
c = 95.867γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-05-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-07-18
    Changes: Non-polymer description
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description