CYTOCHROME bc 1 : A BACTERIAL CYTOCHROME 407
= 2.8, H 2 O · · · H201 N ε 2 = 2.7); (3) the N ζ atom of lys227 ’ s side chain interacts
with the formyl carbonyl group through an intervening water molecule
(O 2 · · · H 2 O = 2.6, H 2 O · · · K227 N ζ = 2.7); and (4) both asp228 carboxylic oxygens
interact with substituents on the salicylate aromatic ring — the amino nitrogen
and the hydroxyl oxygen (N 1 · · · D228 O δ 1 = 2.8, O 1 · · · D228 O δ 2 = 2.6). Confor-
mational details of the antimycin A molecule itself in PDB: 1PPJ differ from
those found in the small molecule structure^94 and in the PDB:1NTK structure.
For instance, an intramolecular hydrogen bond between the phenolic OH
group of the salicylamide ring and the carbonyl oxygen in the amide connector
to the dilactone ring occurs in the small molecule structure and is shown also
in the PDB: 1NTK structure (in PDB: 1NTK, the O 3 · · · O 2 distance = 2.3 Å ).
This intramolecular hydrogen bond was believed to be important for antimy-
cin A binding and inhibitory activity, but this is thrown into question by dif-
ferent fi ndings for the PDB: 1PPJ structure. In PDB: 1PPJ, the amide connector
has fl ipped (rotated approximately 180 ° ) with respect to the salicylamide ring
so that the hydrogen bond is now formed between the phenolic OH and the
NH group of the amide. (O 1 · · · N 2 = 2.6 Å ). See Figure 7.31. Note also that the
side chains of ser35 and lys227 differ in conformation between PDB: 1NTK
and PDB: 1PPJ. This is most evident for lys227 in Figure 7.31.
Figure 7.31 Comparison of antimycin A positions in PDB: 1NTK and PDB: 1PPJ.
Visualized using The PyMOL Molecular Graphics System and ChemDraw Ultra,
version 10.0. (Printed with permission of Delano Scientifi c, LLC and CambridgeSoft
Corporation.) (See color plate)
PDB: 1NTK in cyan.
PDB: 1PPJ in green.his201 ser205lys227asp228ser35helix Dhelix Ahelix Eantimycin A amide
bridge flips