3fll

From Proteopedia

Crystal structure of E55Q mutant of nitrophorin 4

PDB ID 3fll

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Structural highlights

3fll is a 1 chain structure with sequence from Rhodnius prolixus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NP4_RHOPR Heme-based protein that deliver nitric oxide gas (NO) to the victim while feeding, resulting in vasodilation and inhibition of platelet aggregation. Also bind tightly to histamine, which is released by the host to induce wound healing (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Nitrophorins (NPs) are a group of NO-carrying heme proteins found in the saliva of a blood-sucking insect from tropical Central and South America, Rhodnius prolixus, the "kissing bug". NO is kept stable for long periods of time by binding it as an axial ligand to a ferriheme center. The fact that the nitrophorins are stabilized as Fe(III)-NO proteins is a unique property because most heme proteins are readily autoreduced by excess NO and bind NO to the Fe(II) heme irreversibly (K(d)s in the picomolar range). In contrast, the nitrophorins, as Fe(III) heme centers, have K(d)s in the micromolar to nanomolar range and thus allow NO to dissociate upon dilution following injection into the tissues of the victim. This NO can cause vasodilation and thereby allow more blood to be transported to the site of the wound. We prepared 13 site-directed mutants of three major nitrophorins, NP2, NP1, and NP4, to investigate the stabilization of the ferric-NO heme center and preservation of reversible binding that facilitates these proteins' NO storage, transport, and release functions. Of the mutations in which Glu and/or Asp were replaced by Ala, most of these carboxyls show a significant role stabilizing Fe(III)-NO over Fe(II)-NO, with buried E53 of NP2 or E55 of NP1 and NP4 being the most important and partially buried D29 of NP2 or D30 of NP4 being second in importance. The pK(a)s of the carboxyl groups studied vary significantly but all are largely deprotonated at pH 7.5 except E124.

Effect of Mutation of Carboxyl Side-Chain Amino Acids Near the Heme on the Midpoint Potentials and Ligand Binding Constants of Nitrophorin 2 and Its NO, Histamine, and Imidazole Complexes.,Berry RE, Shokhirev MN, Ho AY, Yang F, Shokhireva TK, Zhang H, Weichsel A, Montfort WR, Walker FA J Am Chem Soc. 2009 Jan 28. PMID:19175316^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Berry RE, Shokhirev MN, Ho AY, Yang F, Shokhireva TK, Zhang H, Weichsel A, Montfort WR, Walker FA. Effect of Mutation of Carboxyl Side-Chain Amino Acids Near the Heme on the Midpoint Potentials and Ligand Binding Constants of Nitrophorin 2 and Its NO, Histamine, and Imidazole Complexes. J Am Chem Soc. 2009 Jan 28. PMID:19175316 doi:10.1021/ja808105d