Three-dimensional structures tubulin

Fig. 6. The common pharmacophore of the presented tubulin-binding cytostatic agents is defined by the residues A, B, and C, which are superimposed in the three-dimensional structures.

Fig. 11 Three-dimensional structures of epothilones determined in different environments (O red, S yellow, N dark blue). Top structures of free EpoA determined by X-ray crystallography from dichloromethane/petroleum ether (top left [9 8] (a)) and from methanol/water (top right [143](b)). Bottom structures of EpoA bound to tubulin determined by solution NMR in aqueous medium (bottom left [96]) and by electron crystallography from zinc-stabilized tubulin sheets (bottom right [26]).(a) The crystal structure data have been available from the author to interested research groups since October 1995.(b) H.-J. Hecht, G. Hofle, unpublished results CCDC 241333 and CCDC 241334 contain the crystallographic data of this structure. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retiieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK fax (+ 44) 1223-336-033 or deposit cede. cam. ac. uk)...

Nogales E and Downing K C 1997 Visualizing the secondary structure of tubulin three-dimensional map at 4A J. Struct. Biol. 118 119-27... 

The first structural location of the taxane binding site [42] placed it in the interprotofilament space, thus supporting the biochemical results. However, this changed when the first high resolution 3D structure of the paclitaxel-tubulin complex was solved by electron-crystallography of a two-dimensional zinc-induced tubulin polymer [5]. The fitting of this structure into a three-dimensional reconstruction of microtubules from cryoelectron microscopy allowed a pseudo atomic resolution model of microtubules [43] in which the paclitaxel binding site was placed inside the lumen of the microtubules hidden from the outer solvent. 

All ligand-based molecular modeling studies focusing on agents able to bind the colchicine site were performed before the determination of the X-ray structure of the tubulin-colchicine complex (see below). Computational tools in this field were mainly used to derive three-dimensional QS ARs (through comparative molecular field analysis (CoMFA) and other original approaches), but CSI also constituted useful... 

Figure 4 Correction of improper chromosome attachments by activation of Aurora kinase (45). (a) Assay schematic, (i) Treatment with the Eg5 inhibitor monastrol arrests cells in mitosis with monopolar spindles, in which sister chromosomes often are both attached to the single spindle pole, (ii) Hesperadin, an Aurora kinase inhibitor, is added as monastrol is removed. As the spindle bipolarizes with Aurora kinase inhibited, attachment errors fail to correct so that some sister chromosomes are still attached to the same pole of the bipolar spindle, (iii) Removal of hesperadin activates Aurora kinase. Incorrect attachments are destabilized by disassembling the microtubule fibers, which pulls the chromosomes to the pole, whereas correct attachments are stable, (iv) Chromosomes move from the pole to the center of the spindle as correct attachments form, (b) Structures of the Eg5 inhibitor monastrol and two Aurora kinase inhibitors, hesperadin and AKI-1. (c) Spindles were fixed after bipolarization either in the absence (i) or presence (ii) of an Aurora kinase inhibitor. Arrows indicate sister chromosomes that are both attached to the same spindle pole. Projections of multiple image planes are shown, with optical sections of boxed regions (1 and 2) to highlight attachment errors. Scale bars 5 xm. (d) After the removal of hesperadin, GFP-tubulin (top) and chromosomes (bottom) were imaged live by three-dimensional confocal fluorescence microcopy and DIC, respectively. Arrow and arrowhead show two chromosomes that move to the spindle pole (marked by circle in DIC images) as the associated kinetochore-microtubule fibers shorten and that then move to the center of the spindle. Time (minutes seconds) after the removal of hesperadin. Scale bar 5 (cm.

All three of these proteins are present in the lung. The lamellar bodies are secreted into alveolar lumen where they are transformed into an extracellular form of surfactant that has a quadratic lattice structure called tubular myelin. The three-dimensional tubulin-myelin structures spread in a monolayer at the air-liquid interface. This spreading decreases the surface tension, prevents alveolar collapse at the end of expiration, and confers mechanical stability to the alveoli. The surfactant system is in a continuous state of flux, and surfactant is recycled by uptake... 

Nogales E, Wolf SG, Downing KH (1997) Visualizing the Secondary Structure of Tubulin Three-Dimensional Map at 4 A. J Struct Bio 118 119... 

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