3DXM

Structure of Bos taurus Arp2/3 Complex with Bound Inhibitor CK0993548

Summary for 3DXM

• Entry DOI: 10.2210/pdb3dxm/pdb
• Related: 3DXK
• Descriptor: Actin-related protein 3, Actin-related protein 2, Actin-related protein 2/3 complex subunit 1B, ... (9 entities in total)
• Functional Keywords: beta-propeller, structural protein
• Biological source: Bos taurus; More
• Cellular location: Cytoplasm, cytoskeleton (By similarity): P61157 A7MB62 Q58CQ2 Q3MHR7 Q3T035 Q148J6 Q3SYX9
• Total number of polymer chains: 7
• Total formula weight: 224585.25

Authors

Nolen, B.J.,Tomasevic, N.,Russell, A.,Pierce, D.W.,Jia, Z.,Hartman, J.,Sakowicz, R.,Pollard, T.D. (deposition date: 2008-07-24, release date: 2009-07-28, Last modification date: 2023-08-30)

Primary citation

Nolen, B.J.,Tomasevic, N.,Russell, A.,Pierce, D.W.,Jia, Z.,McCormick, C.D.,Hartman, J.,Sakowicz, R.,Pollard, T.D.
Characterization of two classes of small molecule inhibitors of Arp2/3 complex
Nature, 460:1031-1034, 2009

PubMed Abstract: Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.

PubMed: 19648907
DOI: 10.1038/nature08231

Experimental method

X-RAY DIFFRACTION (2.85 Å)