BIOINORGANIC CHEMISTRY A Short Course Second Edition

398 IRON-CONTAINING PROTEINS AND ENZYMES

to the Q i site (n side, near the matrix space) and inhibits the transfer of elec-
trons from heme b H to ubiquinone, Q.
Before describing inhibitors, we will discuss one X - ray crystallographic
structure that features the substrate substitute ubiquinone - 2, UQ2, in both the
Qo and Q i sites (PDB: 1NTZ).^86 Ubiquinone - 2, UQ2 (see Figure 7.29 ), differs
from UQ10 (see Figure 7.27 ) in having two isoprenoid units in its aliphatic tail
rather than 10 in UQ10. In the Q o pocket, UQ2 is not within hydrogen - bonding
distance ( < 4 Å ) of the aa residues normally associated with inhibitor binding —
that is, the his161 ligand of the [2Fe – 2S] center, glu271 backbone N, or tyr273

Figure 7.29 Cytochrome bc 1 inhibitor structures.

H 3 C

H 3 C N

S

S

N

NH 2

OCH 3

O

H 3 CO

CH 3

CH 3

myxothiazol

dithiazol moiety

methoxy acryl

amide

olefinic tail

R = Hexyl: Antimycin A 1

R = Butyl: Antimycin A 2

atoms involved in hydrogen bonding:

O 1 , N 1 , N 2 , O 2 , O 3 , O 7

O

O

CH 3

OCOCH 2 CH(CH 3 ) 2

H 3 C O R

O

NHCH

C

O

NH

O

H

O

( 1 ) (^2 )

( 1 )

( 7 )

( 5 )

O

O

CH 3

OCOCH 2 CH(CH 3 ) 2

H 3 C O R

O

NHCH

C

O

N

O

H

O

H

( 1 )

( 1 )

( 2 )

( 7 )

( 6 )

H 3 CO

H 3 CO

O

O

CH 2 -CH=C(CH 3 )-(CH 22 )-CH=C(CH 3 ) 2

substitute substrate ubiquinone-2 (UQ2)

( 1 )

( 2 )

( 4 )

O

O

OCH 3

CH 3

H 3 CO

CH 3

H 3 CO

CH 3

OCH 3

CH 3

OH CH 3

Stigmatellin A

chromone rings

PDB:1NTK numbering system PDB: 1PPJ numbering

( 2 ) ( 2 )

( 1 ) numbers in bold in parentheses indicate
numbering system for the atoms in the molecule

( 3 )

( 3 )

atoms involved in hydrogen bonding:

O 1 , N 1 , N 2 , O 2 , O 3

( 8 )

( 5 )

( 4 )

( 3 ) (^1 )

( 1 )

( 2 )

( 1 )

( 2 )