7alr

Crystal structure of TD1-gatorbulin1 complexCrystal structure of TD1-gatorbulin1 complex

Structural highlights 7alr is a 3 chain structure with sequence from Bos taurus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.93Å Ligands: , , , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TBA1B_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. Publication Abstract from PubMed Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at alpha/beta-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the alpha/beta-tubulin-GB1 complex. Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site.,Matthew S, Chen QY, Ratnayake R, Fermaintt CS, Lucena-Agell D, Bonato F, Prota AE, Lim ST, Wang X, Diaz JF, Risinger AL, Paul VJ, Oliva MA, Luesch H Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):e2021847118. doi: , 10.1073/pnas.2021847118. PMID:33619102 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tubulin 3D Structures

spinqualitylabelsall models 7alr, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image