Crystal structures of a nitric oxide transport protein from a blood- sucking insect

Andrzej Weichsel, John F. Andersen, Donald E. Champagne, F. Ann Walker, William "Bill" Montfort

Research output: Contribution to journalArticle

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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 crystal structures of nitrophorin 1 (NP1): bound to cyanide, which binds in a manner similar to NO (2.3 Å resolution); bound to histamine (2.0 Å resolution); and bound to what appears to be NH3 from the crystallization solution (2.0 Å resolution). The NP1 structures reveal heme to be sandwiched between strands of a lipocalin-like β-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 a 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, ~100-fold lower than that for NO.

Original languageEnglish (US)
Pages (from-to)304-309
Number of pages6
JournalNature Structural Biology
Volume5
Issue number4
StatePublished - Apr 1998

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Insects
Carrier Proteins
Nitric Oxide
Blood
Crystal structure
Gases
Histamine
Heme
Rhodnius
Salivary Proteins and Peptides
Lipocalins
Cyanides
Platelets
Crystallization
Platelet Aggregation
Histidine
Vasodilation
Wound Healing
Agglomeration
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Weichsel, A., Andersen, J. F., Champagne, D. E., Walker, F. A., & Montfort, W. B. (1998). Crystal structures of a nitric oxide transport protein from a blood- sucking insect. Nature Structural Biology, 5(4), 304-309.

Crystal structures of a nitric oxide transport protein from a blood- sucking insect. / Weichsel, Andrzej; Andersen, John F.; Champagne, Donald E.; Walker, F. Ann; Montfort, William "Bill".

In: Nature Structural Biology, Vol. 5, No. 4, 04.1998, p. 304-309.

Research output: Contribution to journalArticle

Weichsel, A, Andersen, JF, Champagne, DE, Walker, FA & Montfort, WB 1998, 'Crystal structures of a nitric oxide transport protein from a blood- sucking insect', Nature Structural Biology, vol. 5, no. 4, pp. 304-309.
Weichsel, Andrzej ; Andersen, John F. ; Champagne, Donald E. ; Walker, F. Ann ; Montfort, William "Bill". / Crystal structures of a nitric oxide transport protein from a blood- sucking insect. In: Nature Structural Biology. 1998 ; Vol. 5, No. 4. pp. 304-309.
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