 |
|
Title
|
|
Crystal structures of a nitric oxide transport protein from a blood-sucking insect.
|
|
|
Authors
|
|
A.Weichsel,
J.F.Andersen,
D.E.Champagne,
F.A.Walker,
W.R.Montfort.
|
|
|
Ref.
|
|
Nat Struct Biol, 1998,
5,
304-309.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The nitrophorins are heme-based proteins from the salivary glands of the
blood-sucking insect Rhodnius prolixus that deliver nitric oxide gas (NO) to the
victim while feeding, resulting in vasodilation and inhibition of platelet
aggregation. The nitrophorins also bind tightly to histamine, which is released
by the host to induce wound healing. Here we present three crystal structures of
nitrophorin 1 (NP1): bound to cyanide, which binds in a manner similar to NO
(2.3 A resolution); bound to histamine (2.0 A resolution); and bound to what
appears to be NH3 from the crystallization solution (2.0 A resolution). The NP1
structures reveal heme to be sandwiched between strands of a lipocalin-like
beta-barrel, and in an arrangement unlike any other gas-transport protein
discovered to date. The heme is six-coordinate with a histidine (His 59) on the
proximal side, and ligand in a spacious pocket on the distal side. The
structures confirm that NO and histamine compete for the same binding pocket and
become buried on binding. The dissociation constant for histamine binding was
found to be 19 nM, approximately 100-fold lower than that for NO.
|
|
|
|