Patent ID: 9493527
Filing Date: 2016-11-15
CPC Classification: A61K,A61P,C07K,Y02A,Y10T

Claim Text:
1. An isolated H-NOX protein comprising at least one distal pocket mutation that alters the k off , k 1 , or k 2 for NO, the 0 2 dissociation constant, the NO dissociation constant, or the NO reactivity compared to that of a corresponding wild type H-NOX protein, wherein the H-NOX protein does not comprise a guanylyl cyclase catalytic domain, wherein the distal pocket mutation comprises a substitution at a residue that corresponds to at least one of Thr4, Ile5, Thr9, Trp9, Trp67, Asn74, Ile75, Phe78, Phe82, Tyr140, and Leu144 of a T. tengcongensis H-NOX of SEQ ID NO:54, wherein the mutant H-NOX protein is not Thermoanaerobacter tengcongensis H-NOX Y140L, T. tengcongensis H-NOX W9F, T. tengcongensis H-NOX W9F/Y140L, T. tengcongensis H-NOX F78Y/Y140L, Legionella pneumophilia 2 H-NOX F142Y, Rattus norvegicus sGC 1 H-NOX (1-385) I145Y; and wherein either (a) the k off , k 1 , or k 2 for NO of the H-NOX protein is between about 1×10 −4 s −1 and about 10 s −1 at 37° C., and the 0 2 dissociation constant of the H-NOX protein is at least about 1 M at 37° C., or (b) the NO dissociation constant of the H-NOX protein is within 2 orders of magnitude of that of human hemoglobin alpha, and the NO reactivity of the H-NOX protein is at least 10-fold lower than that of human hemoglobin alpha.