Montfort Lab - Nitrophorins
Nitrophorins 1-4 are from the blood-sucking insect Rhodnius prolixus,
which spreads Chaga's disease. These proteins are named for their ability to transport nitric oxide,
using heme,
from the salivary gland of the insect to the tissue of the host, where the compound induces
vasodilation. Later
studies revealed that the proteins also sequester histamine, which is released by the host in response
to the insect bite, and further revealed that the proteins can interfere with blood coagulation. We have recently
determined the structures of two members of this family - nitrophorins 1 and 4 - and found the protein
to be nearly all beta sheet and completely unlike any other heme-based gas transport protein. Nitric
oxide and histamine compete for the same binding site on the heme, which is wrapped in a lipocalin-like
beta barrel.
Abstracts from recent papers and molecular graphics displays of recent
structures.
A. Weichsel, J.F. Andersen, D.E. Champagne, F.A. Walker, and W.R.
Montfort. Crystal Structure of a Nitric Oxide
Transport Protein from a Blood-Sucking Insect. Nature Structural Biology
(1998), 5:304-309.
J.F. Andersen, D.E. Champagne, A. Weichsel, J.M.C. Ribeiro, C. A. Balfour,
V. Dress, and W.R. Montfort. Nitric oxide binding and crystallization of
recombinant nitrophorin 1, a nitric oxide transport protein from the
blood-sucking bug Rhodnius prolixus. Biochemistry (1997), 36:4423-4428.
J.F. Andersen, A. Weichsel, C. A. Balfour, D.E. Champagne, W.R. Montfort.
The crystal structure of nitrophorin 4 at 1.5 Å resolution: transport of
nitric oxide by a lipocalin-based heme protein. Structure (1998),
6:1315-1327.
X.D. Ding, A. Weichsel, J.F. Andersen, T.Kh. Shokhireva, C. Balfour, A.J. Pierik, B.A. Averill,
W.R. Montfort & A.F. Walker. Nitric oxide binding to the ferri- and
ferroheme states of nitrophorin 1, a reversible NO-binding heme protein from the saliva of
the blood-sucking insect, Rhodnius prolixus. Journal of American Chemical Society
(1999), 121:128-138.
A. Weichsel, J.F. Andersen, S.A. Roberts & W.R. Montfort.
Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial.
Nature Btructural Biology (2000), 7:551-554.
J.F. Andersen, X.D. Ding, C. Balfour, T.Kh. Shokhireva, D.E. Champagne, F.A. Walker & W.R. Montfort.
Kinetics and Equilibria in Ligand Binding by Nitrophorins 1-4:
Evidence for Stabilization of a Nitric Oxide-Ferriheme Complex through a Ligand-Induced
Conformational Trap. Biochemistry (2000), 39:10118-10131.
W.R. Montfort, A. Weichsel & J.F. Andersen. Nitrophorins and Related
Lipocalins from Rhodnius prolixus and Other Blood-Sucking Arthropods.
Biochemica et Biophysica Acta (2000) in press
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Department of Biochemistry
The University of Arizona
Tuesday, October 21st, 1997
montfort@u.arizona.edu
All contents copyright © 1997. All rights reserved. |
