7wmt | pdb_00007wmt

Crystal structure of small molecule 13 bound to human Nicotinamide N-methyltransferase

spinqualitylabelsall models 7wmt, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7wmt is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.77Å Ligands: 1IV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NNMT_HUMAN Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for biotransformation of many drugs and xenobiotic compounds. Publication Abstract from PubMed Recent technological innovations have led to the development of methods for the rapid identification of high-affinity macrocyclic peptides for a wide range of targets; however, it is still challenging to achieve the desired activity and membrane permeability at the same time. Here, we propose a novel small molecule lead discovery strategy, Peptide-to-Small Molecule, which is a combination of rapid identification of high-affinity macrocyclic peptides via peptide display screening followed by pharmacophore-guided de novo design of small molecules, and demonstrate the applicability using nicotinamide N-methyltransferase (NNMT) as a target. Affinity selection by peptide display technology identified macrocyclic peptide 1 that exhibited good enzymatic inhibitory activity but no cell-based activity. Thereafter, a peptide pharmacophore-guided de novo design and further structure-based optimization resulted in highly potent and cell-active small molecule 14 (cell-free IC(50) = 0.0011 muM, cell-based IC(50) = 0.40 muM), indicating that this strategy could be a new option for drug discovery. Peptide-to-Small Molecule: A Pharmacophore-Guided Small Molecule Lead Generation Strategy from High-Affinity Macrocyclic Peptides.,Yoshida S, Uehara S, Kondo N, Takahashi Y, Yamamoto S, Kameda A, Kawagoe S, Inoue N, Yamada M, Yoshimura N, Tachibana Y J Med Chem. 2022 Aug 11;65(15):10655-10673. doi: 10.1021/acs.jmedchem.2c00919. , Epub 2022 Jul 29. PMID:35904556 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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