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| **[[6acr]], [[6gi6]], [[6gip]], [[6gin]], [[4bgg]], [[3q4u]], [[3mtf]], [[6t6d]], [[6jux]], [[6tnb]], [[6tn8]], [[6t8n]], [[6szm]], [[6eix]], [[6srh]], [[5oy6]], [[6z36]], [[6zgc]], [[7a21]], [[7c3g]] - hAcvr1 kinase domain (mutant) + inhibitor<br /> | | **[[6acr]], [[6gi6]], [[6gip]], [[6gin]], [[4bgg]], [[3q4u]], [[3mtf]], [[6t6d]], [[6jux]], [[6tnb]], [[6tn8]], [[6t8n]], [[6szm]], [[6eix]], [[6srh]], [[5oy6]], [[6z36]], [[6zgc]], [[7a21]], [[7c3g]] - hAcvr1 kinase domain (mutant) + inhibitor<br /> |
| **[[3h9r]], [[4c02]], [[6i1s]] - hAcvr1 kinase domain + FKBP12 + inhibitor<br /> | | **[[3h9r]], [[4c02]], [[6i1s]] - hAcvr1 kinase domain + FKBP12 + inhibitor<br /> |
| | **[[7nns]] - hAcvr1 kinase domain + drug<br /> |
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| *Activin receptor type 2 | | *Activin receptor type 2 |
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| **[[4asx]], [[3soc]], [[3q4t]] - hAcvr2A kinase domain + inhibitor<br /> | | **[[4asx]], [[3soc]], [[3q4t]] - hAcvr2A kinase domain + inhibitor<br /> |
| **[[5nh3]] - hAcvr2A LBD + antibody<br /> | | **[[5nh3]] - hAcvr2A LBD + antibody<br /> |
| | **[[7u5p]] - hAcvr2A LBD + inhibin<br /> |
| **[[2goo]], [[2h64]], [[2h62]] - mAcvr2A LBD + BMP-2 + ALK3<br /> | | **[[2goo]], [[2h64]], [[2h62]] - mAcvr2A LBD + BMP-2 + ALK3<br /> |
| **[[1lx5]] - mAcvr2A LBD + BMP-7<br /> | | **[[1lx5]] - mAcvr2A LBD + BMP-7<br /> |
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| **[[2qlu]] - hAcvr2B kinase domain<br /> | | **[[2qlu]] - hAcvr2B kinase domain<br /> |
| **[[5ngv]], [[5nhr]] - hAcvr2B LBD + antibody<br /> | | **[[5ngv]], [[5nhr]] - hAcvr2B LBD + antibody<br /> |
| | **[[7oly]] - hAcvr2B LBD + hAcvr1B LBD + antibody + inhibin<br /> |
| | **[[7mrz]] - hAcvr2B LBD + hAcvr1B LBD + antibody + GDF11<br /> |
| **[[1s4y]] - mAcvr2B LBD + inhibin<br /> | | **[[1s4y]] - mAcvr2B LBD + inhibin<br /> |
| **[[1nyu]] - rAcvr2B LBD + inhibin - rat<br /> | | **[[1nyu]] - rAcvr2B LBD + inhibin - rat<br /> |
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Function
Activin receptors (Acvr) are integral to the activin and myostatin signalling pathway. Binding of activin to the Acvr on muscle cell membrane leads to enhanced muscle protein breakdown and debilitating loss of muscle mass and functional capacity[1].
Disease
A mutation in Acrv1 exists in individuals with the rare developmental disorder fibrodysplasia ossificans progressiva[2].
Relevance
Increased activin/Acvr2 signalling links aging and heart failure pathobiology and that targeted inhibition of this catabolic pathway may form a therapeutic strategy for multiple forms of hear failure[3].
Structural highlights
3D structure of the kinase domain of Acvr1 complex with inhibitor shows the inhibitor forming various interactions with the protein including a hydrogen bonds to His residues and a water bridged hydrogen bond to the catalytic lysine[4]. Water molecule is shown as red sphere.
- ↑ Han HQ, Zhou X, Mitch WE, Goldberg AL. Myostatin/activin pathway antagonism: molecular basis and therapeutic potential. Int J Biochem Cell Biol. 2013 Oct;45(10):2333-47. doi:, 10.1016/j.biocel.2013.05.019. Epub 2013 May 28. PMID:23721881 doi:https://dx.doi.org/10.1016/j.biocel.2013.05.019
- ↑ Williams E, Bullock AN. Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2. Bone. 2017 Sep 12. pii: S8756-3282(17)30340-X. doi: 10.1016/j.bone.2017.09.004. PMID:28918311 doi:https://dx.doi.org/10.1016/j.bone.2017.09.004
- ↑ Roh JD, Hobson R, Chaudhari V, Quintero P, Yeri A, Benson M, Xiao C, Zlotoff D, Bezzerides V, Houstis N, Platt C, Damilano F, Lindman BR, Elmariah S, Biersmith M, Lee SJ, Seidman CE, Seidman JG, Gerszten RE, Lach-Trifilieff E, Glass DJ, Rosenzweig A. Activin type II receptor signaling in cardiac aging and heart failure. Sci Transl Med. 2019 Mar 6;11(482). pii: 11/482/eaau8680. doi:, 10.1126/scitranslmed.aau8680. PMID:30842316 doi:https://dx.doi.org/10.1126/scitranslmed.aau8680
- ↑ Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD, Yu PB. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 2014 Oct 9;57(19):7900-15. doi: 10.1021/jm501177w. Epub 2014 Sep 4. PMID:25101911 doi:https://dx.doi.org/10.1021/jm501177w
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3D structures of activin receptor
Updated on 22-August-2022
{"openlevels":0}
- Activin receptor type 1 or Activin receptor-like type 2 or Serine/threonine-protein kinase receptor R1 or ALK2 or BMP type 1 receptor kinase
- 5oxg - hAcvr1 kinase domain 172-499 + inhibitor - human
- 6acr, 6gi6, 6gip, 6gin, 4bgg, 3q4u, 3mtf, 6t6d, 6jux, 6tnb, 6tn8, 6t8n, 6szm, 6eix, 6srh, 5oy6, 6z36, 6zgc, 7a21, 7c3g - hAcvr1 kinase domain (mutant) + inhibitor
- 3h9r, 4c02, 6i1s - hAcvr1 kinase domain + FKBP12 + inhibitor
- 7nns - hAcvr1 kinase domain + drug
- Activin receptor type 2
- 1bte - Acvr2 LBD 19-134 - mouse
- Activin receptor type 2A
- 4asx, 3soc, 3q4t - hAcvr2A kinase domain + inhibitor
- 5nh3 - hAcvr2A LBD + antibody
- 7u5p - hAcvr2A LBD + inhibin
- 2goo, 2h64, 2h62 - mAcvr2A LBD + BMP-2 + ALK3
- 1lx5 - mAcvr2A LBD + BMP-7
- Activin receptor type 2B
- 2qlu - hAcvr2B kinase domain
- 5ngv, 5nhr - hAcvr2B LBD + antibody
- 7oly - hAcvr2B LBD + hAcvr1B LBD + antibody + inhibin
- 7mrz - hAcvr2B LBD + hAcvr1B LBD + antibody + GDF11
- 1s4y - mAcvr2B LBD + inhibin
- 1nyu - rAcvr2B LBD + inhibin - rat
- 6mac - rAcvr2B LBD + GDF-11 + ALK5
- Activin receptor-like type 1 or Serine/threonine-protein kinase receptor R3 or ALK1
- 2lcr - hALK1 LBD - NMR
- 6sf2 - hALK1 LBD + GDF-2
- 4fao - hALK1 LBD + GDF-2 + SKR3
- 6sf1, 6sf3 - hALK1 LBD + BMP10
- 3my0 - hALK1 kinase domain + inhibitor
References
