3UY9

Bovine trypsin variant X(tripleGlu217Phe227) in complex with small molecule inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.22 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues.

Tziridis, A.Rauh, D.Neumann, P.Kolenko, P.Menzel, A.Brauer, U.Ursel, C.Steinmetzer, P.Sturzebecher, J.Schweinitz, A.Steinmetzer, T.Stubbs, M.T.

(2014) Biol Chem 395: 891-903

  • DOI: https://doi.org/10.1515/hsz-2014-0158
  • Primary Citation of Related Structures:  
    3PLB, 3PLK, 3PLP, 3PM3, 3PMJ, 3PWB, 3PWC, 3PYH, 3Q00, 3UNQ, 3UNS, 3UOP, 3UPE, 3UQO, 3UQV, 3UUZ, 3UWI, 3UY9, 3V12, 3V13

  • PubMed Abstract: 

    A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cationic trypsin
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P
223Bos taurusMutation(s): 10 
EC: 3.4.21.4
UniProt
Find proteins for P00760 (Bos taurus)
Explore P00760 
Go to UniProtKB:  P00760
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BEN
Query on BEN

Download Ideal Coordinates CCD File 
CA [auth F]
EA [auth G]
HA [auth H]
JA [auth I]
LA [auth J]
CA [auth F],
EA [auth G],
HA [auth H],
JA [auth I],
LA [auth J],
NA [auth K],
PA [auth L],
R [auth A],
RA [auth M],
T [auth B],
TA [auth N],
V [auth C],
VA [auth O],
X [auth D],
XA [auth P],
Z [auth E]
BENZAMIDINE
C7 H8 N2
PXXJHWLDUBFPOL-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
BA [auth F]
DA [auth G]
FA [auth H]
IA [auth I]
KA [auth J]
BA [auth F],
DA [auth G],
FA [auth H],
IA [auth I],
KA [auth J],
MA [auth K],
OA [auth L],
Q [auth A],
QA [auth M],
S [auth B],
SA [auth N],
U [auth C],
UA [auth O],
W [auth D],
WA [auth P],
Y [auth E]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
AA [auth E],
GA [auth H],
YA [auth P]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.22 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.069α = 89.62
b = 98.569β = 88.85
c = 120.781γ = 103.99
Software Package:
Software NamePurpose
DENZOdata reduction
AMoREphasing
REFMACrefinement
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-12
    Type: Initial release
  • Version 1.1: 2014-07-16
    Changes: Database references
  • Version 1.2: 2018-12-05
    Changes: Data collection, Source and taxonomy
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description