4x3v

Crystal structure of human ribonucleotide reductase 1 bound to inhibitorCrystal structure of human ribonucleotide reductase 1 bound to inhibitor

Structural highlights 4x3v is a 2 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 3.7Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RIR1_HUMAN Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Publication Abstract from PubMed Ribonucleotide reductase (RR) catalyzes the rate-limiting step of dNTP synthesis and is an established cancer target. Drugs targeting RR are mainly nucleoside in nature. In this study, we sought to identify non-nucleoside small-molecule inhibitors of RR. Using virtual screening, binding affinity, inhibition, and cell toxicity, we have discovered a class of small molecules that alter the equilibrium of inactive hexamers of RR, leading to its inhibition. Several unique chemical categories, including a phthalimide derivative, show micromolar IC50s and KDs while demonstrating cytotoxicity. A crystal structure of an active phthalimide binding at the targeted interface supports the noncompetitive mode of inhibition determined by kinetic studies. Furthermore, the phthalimide shifts the equilibrium from dimer to hexamer. Together, these data identify several novel non-nucleoside inhibitors of human RR which act by stabilizing the inactive form of the enzyme. Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators.,Ahmad MF, Huff SE, Pink J, Alam I, Zhang A, Perry K, Harris ME, Misko T, Porwal SK, Oleinick NL, Miyagi M, Viswanathan R, Dealwis CG J Med Chem. 2015 Dec 24;58(24):9498-509. doi: 10.1021/acs.jmedchem.5b00929. Epub , 2015 Dec 9. PMID:26488902 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonucleotide reductase 3D structures

spinqualitylabelsall models 4x3v, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image