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| CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease. <ref>PMID:11893336</ref> | | CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease. <ref>PMID:11893336</ref> |
| *<scene name='51/517369/Cv/4'>1st Ca+2 coordination site</scene>. Water molecules are shown as red spheres. | | *<scene name='51/517369/Cv/7'>Inhibitor binding site</scene>. Water molecules are shown as red spheres. |
| | *<scene name='51/517369/Cv/8'>Covalent bond between Cys 115 of human calpain1 large subunit with inhibitor</scene>. |
| | *<scene name='51/517369/Cv/4'>1st Ca+2 coordination site</scene>. |
| *<scene name='51/517369/Cv/5'>2nd Ca+2 coordination site</scene>.<ref>PMID:16411745</ref> | | *<scene name='51/517369/Cv/5'>2nd Ca+2 coordination site</scene>.<ref>PMID:16411745</ref> |
| </StructureSection> | | </StructureSection> |
Revision as of 12:22, 9 January 2019
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Function
Calpains (CAP) are calcium-dependent cysteine proteases. CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin.[1] The CAP family contains 14 members.
- CAP1 (or mu-CAP) and CAP2 (or M-CAP) T are the best characterized CAPs.
- CAP7 is atypical CAP that lacks a penta-EF-hand domain.
- CAP8 and CAP9 are involved in the mucosal defense against stress-induced gastropathies.
- CAP9 has been identified as the tumor suppressor for gastric cancer.
- CAP13 is expressed in testis and lungs.
Disease
CAP3 defects lead to a certain muscular dystrophy. Defective CAPs have a role in neurodegeneration.
Structural highlights
CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease. [2]
- ↑ Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:https://dx.doi.org/10.1152/physrev.00029.2002
- ↑ Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL. A Ca(2+) switch aligns the active site of calpain. Cell. 2002 Mar 8;108(5):649-60. PMID:11893336
- ↑ Li Q, Hanzlik RP, Weaver RF, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745 doi:https://dx.doi.org/10.1021/bi052077b
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3D structures of calpain
Updated on 09-January-2019
{"openlevels":0}
- CAP small subunit
- 1aj5– rCAP domain VI – rat
- 1dvi - rCAP domain VI + Ca
- 1np8 – rCAP residues 87-245 - Cd
- 1alv, 1nx2 - pCAP domain VI + Ca – pig
- 1alw, 1nx3 - pCAP domain VI + Ca+ inhibitor
- 1nx0 - pCAP domain VI + Ca+ Calpastatin peptide + small molecule inhibitor peptide
- 1nx1 - pCAP domain VI + Ca+ Calpastatin peptide
- 4phj – hCAP EF-hand subunit + Ca - human
- 4phk, 4phm, 4phn, 4wq2, 4wq3, 5d69 – hCAP EF-hand subunit + Ca + inhibitor
- CAP1
- 1kxr, 1tlo, 1qxp - rCAP protease domain + Ca
- 1tl9 - rCAP protease domain + Ca+ leupeptin inhibitor
- 2g8e, 2g8j, 2nqg, 2nqi, 2r9c, 2r9f - rCAP protease domain + Ca+ inhibitor
- 2ary - hCAP protease domain + Ca
- 1zcm - hCAP protease domain (mutant) + Ca+ inhibitor
- CAP2
- 1mdw – rCAP2 protease core domain I and II (mutant) + Ca
- 1df0, 1u5i – rCAP small subunit domain VI + rCAP2 large subunit
- 3df0 - hCAP small subunit + hCAP2 large subunit + Calpastatin + Ca
- 3bow - rCAP small subunit + rCAP2 large subunit + Calpastatin + Ca
- 1kfu, 1kfx – hCAP small subunit + hCAP2 large subunit
- CAP3
- 4okh - hCAP EF-hand domain residues 642-821
- 6bdt, 6bgp - hCAP residues 46-419 (mutant)
- 6bjd - hCAP residues 46-419 + sorbitol + guanidine derivative
- 6bkj - hCAP residues 46-419 + leupeptin peptide
- CAP7
- 2qfe - hCAP C2-like domain
- CAP8
- 2nqa - hCAP protease domain + Ca+ leupeptin inhibitor
- CAP9
- 1ziv – hCAP catalytic domain
- 2p0r - hCAP protease domain + Ca+ leupeptin inhibitor
- CAP13
- 2i7a – hCAP domain IV + Ca
References
