Human Cytochrome P450 3A5 (CYP3A5)

Experimental Data Snapshot

  • Resolution: 2.91 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report

Ligand Structure Quality Assessment 

This is version 1.4 of the entry. See complete history


The X-Ray Crystal Structure of the Human Mono-Oxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5.

Hsu, M.H.Savas, U.Johnson, E.F.

(2018) Mol Pharmacol 93: 14-24

  • DOI: https://doi.org/10.1124/mol.117.109744
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 

    The contributions of cytochrome P450 3A5 to the metabolic clearance of marketed drugs is unclear, but its probable role is to augment the metabolism of several drugs that are largely cleared by P450 3A4. Selective metabolism by 3A4 is often a concern in drug development owing to potential drug-drug interactions and the variability of 3A4 and 3A5 expression. The contribution of P450 3A5 to these clearance pathways varies between individuals owing to genetic differences and similarities and differences in the metabolic properties of 3A5 compared with 3A4. To better understand the structural differences between P450s 3A4 and 3A5, the structure of 3A5 complexed with ritonavir was determined by X-ray crystallography to a limiting resolution of 2.91 Å. The secondary and tertiary structures of 3A5 and 3A4 are similar, but the architectures of their active sites differ. The 3A5 active site is taller and narrower than that of 3A4. As a result, ritonavir adopts a distinctly different conformation to fit into the cavity of 3A5 than seen for 3A4. These structural changes reflect amino acid differences that alter the conformation of the helix F through helix G region in the upper portion of the cavity and ionic interactions between residues in the beta-sheet domain that reduce the width of the cavity. The structural differences exhibited by 3A4 and 3A5 suggest that the overlap of catalytic activities may reflect molecular flexibility that determines how alternative conformers fit into the different active site architectures of the two enzymes.

  • Organizational Affiliation

    Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California.

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytochrome P450 3A5
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L
480Homo sapiensMutation(s): 0 
Gene Names: CYP3A5
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P20815 (Homo sapiens)
Explore P20815 
Go to UniProtKB:  P20815
GTEx:  ENSG00000106258 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20815
Sequence Annotations
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Query on RIT

Download Ideal Coordinates CCD File 
N [auth A],
P [auth B],
W [auth H]
C37 H48 N6 O5 S2
Query on HEM

Download Ideal Coordinates CCD File 
AA [auth L]
M [auth A]
O [auth B]
Q [auth C]
R [auth D]
AA [auth L],
M [auth A],
O [auth B],
Q [auth C],
R [auth D],
S [auth E],
T [auth F],
U [auth G],
V [auth H],
X [auth I],
Y [auth J],
Z [auth K]
C34 H32 Fe N4 O4
Binding Affinity Annotations 
IDSourceBinding Affinity
RIT BindingDB:  5VEU Ki: 120 (nM) from 1 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Resolution: 2.91 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 148.988α = 90
b = 198.384β = 90
c = 234.881γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
Aimlessdata scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment 

Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM031001

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-15
    Type: Initial release
  • Version 1.1: 2017-12-13
    Changes: Database references
  • Version 1.2: 2018-01-10
    Changes: Structure summary
  • Version 1.3: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.4: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description