PDBsum entry 6zwc

Cell cycle

PDB id: 6zwc

Contents

Protein chains

436 a.a.

431 a.a.

155 a.a.

Ligands

GTP

GDP

QRQ

Metals

_MG

Waters ×233

PDB id:

6zwc

Name:

Cell cycle

Title:

Z-sbtub2 photoswitch bound to tubulin-darpin d1 complex

Structure:

Tubulin alpha-1b chain. Chain: a. Synonym: alpha-tubulin ubiquitous,tubulin k-alpha-1,tubulin alpha- ubiquitous chain. Tubulin beta-2b chain. Chain: b. Designed ankyrin repeat protein (darpin) d1. Chain: f. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Bovine. Synthetic construct. Organism_taxid: 32630. Expressed in: synthetic construct. Expression_system_taxid: 32630

Resolution:

2.04Å R-factor: 0.227 R-free: 0.282

Authors:

M.Wranik,T.Weinert,N.Olieric,L.Gao,Y.C.M.Kraus,R.Bingham,E.Ntouliou, J.Ahlfeld,O.Thorn-Seshold,M.O.Steinmetz,J.Standfuss

Key ref:

L.Gao et al. (2021). A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton. Cell Chem Biol, 28, 228. PubMed id: 33275880 DOI: 10.1016/j.chembiol.2020.11.007

Date:

28-Jul-20 Release date: 23-Dec-20

Protein chain

P81947  (TBA1B_BOVIN) -  Tubulin alpha-1B chain from Bos taurus

Seq: 451 a.a.

Struc: 436 a.a.

Protein chain

Q6B856  (TBB2B_BOVIN) -  Tubulin beta-2B chain from Bos taurus

Seq: 445 a.a.

Struc: 431 a.a.

Protein chain

No UniProt id for this chain

Struc: 155 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.6.5.- - ?????
• Enzyme class 3: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1016/j.chembiol.2020.11.007

Cell Chem Biol 28:228 (2021)

PubMed id: 33275880

A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton.

L.Gao, J.C.M.Meiring, Y.Kraus, M.Wranik, T.Weinert, S.D.Pritzl, R.Bingham, E.Ntouliou, K.I.Jansen, N.Olieric, J.Standfuss, L.C.Kapitein, T.Lohmüller, J.Ahlfeld, A.Akhmanova, M.O.Steinmetz, O.Thorn-Seshold.

ABSTRACT

Optically controlled chemical reagents, termed "photopharmaceuticals," are powerful tools for precise spatiotemporal control of proteins particularly when genetic methods, such as knockouts or optogenetics are not viable options. However, current photopharmaceutical scaffolds, such as azobenzenes are intolerant of GFP/YFP imaging and are metabolically labile, posing severe limitations for biological use. We rationally designed a photoswitchable "SBT" scaffold to overcome these problems, then derivatized it to create exceptionally metabolically robust and fully GFP/YFP-orthogonal "SBTub" photopharmaceutical tubulin inhibitors. Lead compound SBTub3 allows temporally reversible, cell-precise, and even subcellularly precise photomodulation of microtubule dynamics, organization, and microtubule-dependent processes. By overcoming the previous limitations of microtubule photopharmaceuticals, SBTubs offer powerful applications in cell biology, and their robustness and druglikeness are favorable for intracellular biological control in in vivo applications. We furthermore expect that the robustness and imaging orthogonality of the SBT scaffold will inspire other derivatizations directed at extending the photocontrol of a range of other biological targets.