3HQD

Human kinesin Eg5 motor domain in complex with AMPPNP and Mg2+

Summary for 3HQD

• Entry DOI: 10.2210/pdb3hqd/pdb
• Related: 1ii6 1q0b 1x88 2ieh
• Descriptor: Kinesin-like protein KIF11, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: kinesin, motor domain, atp hydrolysis, mitosis, spindle protein, atp-binding, cell cycle, cell division, coiled coil, microtubule, motor protein, nucleotide-binding, phosphoprotein, polymorphism
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P52732
• Total number of polymer chains: 2
• Total formula weight: 83493.45

Authors

Parke, C.L.,Wojcik, E.J.,Kim, S.,Worthylake, D.K. (deposition date: 2009-06-05, release date: 2009-12-08, Last modification date: 2023-09-06)

Primary citation

Parke, C.L.,Wojcik, E.J.,Kim, S.,Worthylake, D.K.
ATP Hydrolysis in Eg5 Kinesin Involves a Catalytic Two-water Mechanism.
J.Biol.Chem., 285:5859-5867, 2010

PubMed Abstract: Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

PubMed: 20018897
DOI: 10.1074/jbc.M109.071233

Experimental method

X-RAY DIFFRACTION (2.19 Å)