1x8p
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0.85 A Crystal Structure Of Nitrophorin 4 From Rhodnius Prolixus Complexed With Ammonia at pH 7.4
OverviewOverview
The blood-sucking insect Rhodnius prolixus uses nitrophorin 4, a heme, protein, to deliver nitric oxide (NO) to a victim, causing vasodilation, and improved feeding. Binding of NO occurs at a ferric heme and is, modulated by pH. NO binding at lower pH induces a large conformational, change involving loops A-B and G-H that leads to distal pocket desolvation, and protection of the nitrosyl heme complex. We have determined the, crystal structures of Rhodnius nitrophorin 4 to ultrahigh resolution in, four functional states: +/-NO at pH = 7.4 and +/-NO at pH = 5.6. The, structure with NO at pH 7.4 (1.08 A) is newly determined while the other, complexes have been modeled to resolutions much greater than previously, reported (1.0-0.85 A). The ultrahigh resolution allowed us to resolve, multiple conformers in binding-site loops, leading to a detailed, description of the dynamics involved with storing NO in the insect, salivary gland at low pH, and releasing NO in response to the increased pH, of a victim's tissue. Strikingly, features for both the "open" and, "closed" conformers exist under all conditions, suggesting that the, flexible loops can transition with relative ease between conformational, states. Yet, release of NO from rNP4 is much slower than found for other, ferric heme proteins. The structures suggest that highly mobile loops can, limit diffusion of diatomic molecules into and out of a protein cavity, a, result with implications for the role of protein dynamics in function.
About this StructureAbout this Structure
1X8P is a Single protein structure of sequence from Rhodnius prolixus with HEM and NH3 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Protein functional cycle viewed at atomic resolution: conformational change and mobility in nitrophorin 4 as a function of pH and NO binding., Kondrashov DA, Roberts SA, Weichsel A, Montfort WR, Biochemistry. 2004 Nov 2;43(43):13637-47. PMID:15504026
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