4fxy

Crystal structure of rat neurolysin with bound pyrazolidin inhibitor

spinqualitylabelsall models 4fxy, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fxy is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0W2, ZN Related: 1i1i, 2o3e Gene: Nln (Buffalo rat) Activity: Neurolysin, with EC number 3.4.24.16 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NEUL_RAT] Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Publication Abstract from PubMed Neuropeptidases specialize in the hydrolysis of the small bioactive peptides that play a variety of signaling roles in the nervous and endocrine systems. One neuropeptidase, neurolysin, helps control the levels of the dopaminergic circuit modulator neurotensin and is a member of a fold group that includes the antihypertensive target angiotensin converting enzyme. We report the discovery of a potent inhibitor that, unexpectedly, binds away from the enzyme catalytic site. The location of the bound inhibitor suggests it disrupts activity by preventing a hinge-like motion associated with substrate binding and catalysis. In support of this model, the inhibition kinetics are mixed, with both noncompetitive and competitive components, and fluorescence polarization shows directly that the inhibitor reverses a substrate-associated conformational change. This new type of inhibition may have widespread utility in targeting neuropeptidases. Allosteric Inhibition of the Neuropeptidase Neurolysin.,Hines CS, Ray K, Schmidt JJ, Xiong F, Feenstra RW, Pras-Raves M, de Moes JP, Lange JH, Melikishvili M, Fried MG, Mortenson P, Charlton M, Patel Y, Courtney SM, Kruse CG, Rodgers DW J Biol Chem. 2014 Nov 5. pii: jbc.M114.620930. PMID:25378390 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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