5m6k
Crystal structure of nitrophorin 7 E27V mutant from Rhodnius prolixus with imidazole
Structural highlights
FunctionNP7_RHOPR Converts nitrite as the sole substrate to form nitric oxide gas (NO). NO(2-) serves both as an electron donor and as an electron acceptor. Binds to negatively charged cell surfaces of activated platelets; binds to L-a-phosphatidyl-L-serine (PS)-bearing phospholipid membranes. Once bound on an activated platelet, NP7 releases its stored nitric oxide gas (NO) into the victim's tissues while feeding, resulting in vasodilation and inhibition of platelet aggregation. Also acts as an anticoagulant by blocking coagulation-factor binding sites. Has antihistamine activity; binds histamine with high affinity.[1] [2] [3] [4] [5] Publication Abstract from PubMedNitrophorins (NP) 1-7 are NO-carrying heme proteins found in the saliva of the blood-sucking insect Rhodnius prolixus. The isoform NP7 displays peculiar properties, such as an abnormally high isoelectric point, the ability to bind negatively charged membranes, and a strong pH sensitivity of NO affinity. A unique trait of NP7 is the presence of Glu in position 27, which is occupied by Val in other NPs. Glu27 appears to be important for tuning the heme properties, but its influence on the pH-dependent NO release mechanism, which is assisted by a conformational change in the AB loop, remains unexplored. Here, in order to gain insight into the functional role of Glu27, we examine the effect of Glu27 --> Val and Glu27 --> Gln mutations on the ligand binding kinetics using CO as a model. The results reveal that annihilation of the negative charge of Glu27 upon mutation reduces the pH sensitivity of the ligand binding rate, a process that in turn depends on the ionization of Asp32. We propose that Glu27 exerts a through-space electrostatic action on Asp32, which shifts the pKa of the latter amino acid towards more acidic values thus reducing the pH sensitivity of the transition between open and closed states. Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.,Abbruzzetti S, Allegri A, Bidon-Chanal A, Ogata H, Soavi G, Cerullo G, Bruno S, Montali C, Luque FJ, Viappiani C Sci Rep. 2018 Jul 18;8(1):10855. doi: 10.1038/s41598-018-29182-3. PMID:30022039[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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