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| <StructureSection load='' size='400' side='right' scene='41/417543/Cv/1' caption='Yeast proteasome 20S core complex with salinosporamide derivative, [[3gpt]]'> | | <StructureSection load='' size='350' side='right' scene='41/417543/Cv/1' caption='Yeast proteasome 20S core complex with salinosporamide derivative, [[3gpt]]'> |
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| == Function == | | == Function == |
| [[Proteasome]] (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides<ref>PMID:22350895</ref>. The '''26S PRTS''' is composed of a central '''20S core particle''' which contains 4 stacked rings each with several members and two 19S caps. The 19S cap is composed of a base with 10 proteins six of which are ATPases and a lid which contains 9 proteins which bind polyubiquitin. <br /> | | [[Proteasome]] (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides<ref>PMID:22350895</ref>. The '''26S PRTS''' is composed of a central '''20S core particle''' which contains 4 stacked rings each with several members and two 19S caps. The 19S cap is composed of a base with 10 proteins six of which are ATPases and a lid which contains 9 proteins which bind polyubiquitin. <br /> |
| | *'''13S PRTS''' is a PRTS core intermediate containing α ring, partial β ring and 3 chaperones<ref>PMID:33846632</ref>. |
| | *'''15S PRTS''' is half of an 20S PRTS and upon dimerisation forms the mature 20S PRTS<ref>PMID:32442437</ref>. |
| For more details see [[3unb]]. | | For more details see [[3unb]]. |
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| The core particle two outer rings contain 7 α subunits (Y7, Y13, PRE6, PRE5, PUP2, C1, C7-α) which form the PRTS gate. The two inner rings contain 7 β subunits (PRE2, PRE4, PRE3, PUP1, PUP3, C5, C11) with protease activity<ref>PMID:8811196</ref>. | | The core particle two outer rings contain 7 α subunits (Y7, Y13, PRE6, PRE5, PUP2, C1, C7-α) which form the PRTS gate. The two inner rings contain 7 β subunits (PRE2, PRE4, PRE3, PUP1, PUP3, C5, C11) with protease activity<ref>PMID:8811196</ref>. |
| *<scene name='41/417543/Cv/2'>α subunits and β subunits</scene>. | | *<scene name='41/417543/Cv/2'>α subunits and β subunits</scene>. |
| *<scene name='41/417543/Cv/4'>Salinosporamide derivative binding site</scene> of chain H. | | *<scene name='41/417543/Cv/6'>Salinosporamide derivative binding site</scene> of chain H. |
| *<scene name='41/417543/Cv/5'>Covalent bond between Salinosporamide derivative and Thr1</scene>. | | *<scene name='41/417543/Cv/7'>Covalent bond between Salinosporamide derivative and Thr1</scene>. |
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| | == 3D Structures of Proteasome == |
| | [[Proteasome 3D structures]] |
| | == See Also == |
| | [[PROTAC]] (Proteolysis-Targeting Chimera), an alternative to conventional enzyme inhibitors, by enabling proteasome induced degradation of the target protein. |
| </StructureSection> | | </StructureSection> |
| == 3D Structures of Proteasome ==
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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| {{#tree:id=OrganizedByTopic|openlevels=0|
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| * Proteasome 20S particle
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| **[[3mfe]], [[3mi0]], [[2fhg]] – Mt20S core – ''Mycobacterium tuberculosis''<br />
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| **[[3gpt]], [[3gpw]], [[1g0u]], [[5cz4]] – y20S core - yeast<br />
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| **[[1ryp]], [[3wxr]], [[4qux]], [[4quy]], [[4qv0]], [[4qv1]], [[4qv3]], [[4qv4]], [[4qv5]], [[4qv6]], [[4qv7]], [[4qv8]], [[4qv9]], [[4y8r]], [[4y9y]], [[4ya1]], [[4ya4]], [[5bxl]], [[5cgf]], [[5cza]], [[5d0w]], [[5fg7]], [[5fg9]], [[5fga]] - y20S core (mutant)<br />
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| **[[4r3o]], [[5le5]], [[5lex]] – h20S – human<br />
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| **[[3mka]], [[3hfa]] – Mt20S core (mutant)<br />
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| **[[3c91]], [[3c92]], [[1pma]], [[3j9i]], [[5vy3]] – Ta20S core - ''Themoplasma acidophilum'' - Cryo EM<br />
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| **[[3h4p]] – 20S core – ''Methanocaldococcus janaschii''<br />
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| **[[2h6j]], [[1q5r]] – Re20S core (mutant) – ''Rhodococcus erythropolis''<br />
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| **[[1q5q]] - Re20S core<br />
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| **[[1j2q]] – Af20S core - ''Archaeoglobus fulgidus''<br />
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| **[[1iru]] – 20S core - bovine<br />
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| **[[3une]] – m20S core – mouse<br />
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| **[[3unh]] – m20S core (immuno)
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| *Proteasome 20S+activator protein
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| **[[4v7o]], [[5nif]] – y20S core+ Blm10 <br />
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| **[[1z7q]], [[1fnt]] – y20S core+PA26<br />
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| **[[3ipm]], [[3jrm]], [[3jse]], [[3jtl]], [[1ya7]], [[1yar]], [[1yau]] - Taa-PRTS chains A-G+ Tab-PRTS chains H-N+PA26 chains O-U <br />
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| **[[5lzp]] - Mt20S subunits a+b + BPA - Cryo EM<br />
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| *Proteasome 20S+inhibitor
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| **[[3hye]], [[3gpj]], [[3dy3]], [[3dy4]], [[3e47]], [[3d29]], [[3bdm]], [[2zcy]], [[2gpl]], [[2fak]], [[2f16]], [[1jd2]], [[1g65]], [[3mg0]], [[3mg4]], [[3mg6]], [[3mg7]], [[3mg8]], [[3oeu]], [[3oev]], [[3okj]], [[3shj]], [[3un4]], [[3un8]], [[3sdi]], [[3sdk]], [[4fzc]], [[4fzg]], [[4gk7]], [[4eu2]], [[4inr]], [[4int]], [[4inu]], [[4jsq]], [[4jsu]], [[4jt0]], [[4qwx]], [[4qzz]], [[4r17]], [[4r18]], [[4rur]], [[5ahj]], [[4y69]], [[4y6v]], [[4y6z]], [[4y70]], [[4y74]], [[4y75]], [[4y77]], [[4y78]], [[4y7w]], [[4y7x]], [[4y7y]], [[4y80]], [[4y81]], [[4y82]], [[4y8g]], [[4y8h]], [[4y8i]], [[4y8j]], [[4y8k]], [[4y8l]], [[4y8m]], [[5dki]], [[5dkj]], [[5l52]], [[5l54]], [[5l55]], [[4y6a]], [[4y84]], [[4y8n]], [[4y8o]], [[4y8p]], [[4y8q]], [[4y8s]], [[4y8t]], [[4y8u]], [[4y9z]], [[4ya0]], [[4ya2]], [[4ya3]], [[4ya5]], [[4ya7]], [[4ya9]], [[4z1l]], [[5jhr]], [[5jhs]], [[5lai]], [[4r02]], [[2zcy]], [[5bou]], [[5laj]] – y20S core+inhibitor<br />
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| **[[4qxj]], [[4qz0]], [[4qz1]], [[4qz2]], [[4qz3]], [[4qz4]], [[4qz5]], [[4qz6]], [[4qz7]], [[4qzw]], [[4qzx]], [[4r00]], [[4r02]], [[5bxn]], [[5cgg]], [[5cgh]], [[5cgi]], [[5cz5]], [[5d05]], [[5d0s]], [[5d0t]], [[5d0v]], [[5d0x]], [[5d0z]], [[5fgh]], [[4r00]] – y20S (mutant) + inhibitor<br />
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| **[[3tdd]], [[4j70]] - y20S core + belactosin<br />
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| **[[4hnp]], [[4hrc]], [[4hrd]], [[4lqi]], [[4ltc]], [[4q1s]] - y20S core + antibiotics<br />
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| **[[4nnn]], [[4nnw]], [[4no1]], [[4no6]], [[4no8]], [[4no9]], [[4qby]], [[4qlq]], [[4qls]], [[4qlt]], [[4qlu]], [[4qlv]] - y20S core+ peptide inhibitor<br />
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| **[[5cz6]], [[5cz7]] - y20S (mutant) + peptide inhibitor<br />
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| **[[3h6f]], [[3h6i]], [[3hf9]], [[2fhh]], [[3krd]] – Mt20S core+inhibitor<br />
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| **[[3nzj]], [[3nzw]], [[3nzx]] - y20S + TMC-95A mimic ligand<br />
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| **[[4qvl]], [[4qw4]] – y20S + lymphoma drug<br />
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| **[[4qvm]], [[4qvn]], [[4qvp]], [[4qvq]], [[4qvv]], [[4qvw]], [[4qvy]], [[4qw0]], [[4qw1]], [[4qw3]], [[4qw5]], [[4qw6]], [[4qw7]], [[4qwf]], [[4qwg]], [[4qwi]], [[4qwj]], [[4qwk]], [[4qwl]], [[4qwr]], [[4qws]], [[4qwu]] – y20S (mutant) + lymphoma drug<br />
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| **[[5cz8]], [[5cz9]], [[5fgd]], [[5fge]], [[5fgf]], [[5fgg]], [[5fgi]], [[5fhs]] - y20S (mutant) + cancer drug<br />
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| **[[4r67]] – h20S + cancer drug<br />
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| **[[4x6z]] - y20S + modulator<br />
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| **[[5gjq]] - y20S + ubiquitin carboxyl hydrolase 14 + polyubiquitin<br />
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| **[[5l5a]] - y20S + h20S beta5i<br />
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| **[[5ltt]] - y20S + h20S beta5i + inhibitor<br />
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| **[[5l5b]], [[5l5r]] - y20S + h20S beta5i + h20S beta6<br />
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| **[[5l5w]] - y20S + h20S beta5c + h20S beta6<br />
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| **[[5l5x]], [[5l60]], [[5l61]] - y20S + h20S beta5c + h20S beta6 + inhibitor<br />
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| **[[5l5y]], [[5l5z]] - y20S + h20S beta5c + h20S beta6 + cancer drug<br />
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| **[[5l5d]], [[5l5h]], [[5l5q]], [[5l5i]], [[5l5j]], [[5l5o]], [[5l5p]], [[5l5s]], [[5l5t]], [[5l5u]], [[5l5v]], [[5l62]], [[5l63]], [[5l64]], [[5l68]], [[5l69]], [[5l6a]], [[5l6c]], [[5m2b]] - y20S + h20S beta5i + h20S beta6 + inhibitor<br />
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| **[[5l5e]], [[5l5f]] - y20S + h20S beta5i + h20S beta6 + cancer drug<br />
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| **[[5l65]], [[5l66]] - y20S + m20S beta5i + m20S beta6 + cancer drug<br />
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| **[[5l67]], [[5l6b]] - y20S + m20S beta5i + m20S beta6 + inhibitor<br />
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| **[[3unb]], [[3unf]] – m20S + inhibitor<br />
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| **[[5ley]], [[5lf0]], [[5lf1]], [[5lf3]], [[5lf4]], [[5lf7]], [[5lez]], [[5lf6]] - h20S + inhibitor<br />
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| **[[5a0q]] - h20S + substrate analog<br />
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| **[[5fmg]] - Pf20S + inhibitor - ''Plasmodium falciparum'' - Cryo EM<br />
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| **[[5trr]], [[5trs]], [[5try]], [[5ts0]], [[5tho]], [[5trg]] - Mt20S + peptide<br />
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| * Proteasome partial 20S particle
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| **[[2ku1]], [[2ku2]] – Taa-PRTS chains A-G <br />
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| **[[3fp9]] – MtATPase chains A-L<br />
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| **[[1j2p]] – Af α subunit<br />
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| **[[2jay]] – Mt β subunit<br />
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| **[[2kqz]], [[2kr0]] – hPRTS ubiquitin receptor domain
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| *Proteasome partial 26S particle
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| **[[5l4k]] - hPRTS lid - CryoEM<br />
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| **[[5dsv]] - hPRTS subunit a type-3<br />
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| **[[1p9c]] – hPRTS subunit 4 C-terminal<br />
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| **[[1p9d]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain<br />
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| **[[1uel]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain - NMR<br />
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| **[[1yx4]] - hPRTS subunit 4 – NMR<br />
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| **[[1yx5]], [[1yx6]], [[2kde]], [[2kdf]] - hPRTS subunit 4+ubiquitin – NMR<br />
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| **[[2o95]], [[2o96]] - hPRTS subunit 7<br />
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| **[[3kw6]] - hPRTS subunit 8<br />
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| **[[2krk]] - hPRTS subunit 8 – NMR<br />
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| **[[1qym]], [[1uoh]] - hPRTS subunit 10<br />
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| **[[1tr4]] - hPRTS subunit 10 – NMR<br />
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| **[[4nik]] - hPRTS subunit 10 + single-chain Fv<br />
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| **[[3t5x]] - hPRTS subunit Dss1 + PCI domain-containing protein 2<br />
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| **[[2dvw]], [[2dwz]] - mPRTS subunit 10 + hPRTS subunit 6B – mouse<br />
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| **[[3aji]] - mPRTS subunit 10 + subunit 4<br />
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| **[[2x5n]] - PRTS subunit RPN10 VWA domain – fission yeast<br />
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| **[[4ady]] - yPRTS subunit RPN2<br />
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| **[[3vlf]] - yPRTS subunit 7 + DNA mismatch repair protein<br />
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| **[[2mr3]] - yPRTS subunit RPN9 – NMR<br />
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| **[[2mqw]] - yPRTS subunit RPN9 N terminal – NMR<br />
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| **[[2mri]] - yPRTS subunit RPN9 C terminal – NMR<br />
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| **[[4b0z]] - yPRTS subunit RPN12<br />
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| **[[2z4d]] - yPRTS subunit RPN13<br />
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| **[[3vl1]] - yPRTS subunit RPN14 (mutant)<br />
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| **[[4o8x]], [[4o8y]] - yPRTS subunit RPN8 + RPN11<br />
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| **[[4ocl]], [[4ocm]], [[4ocn]] - yPRTS subunit RPN8 + RPN11 + nanobody<br />
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| **[[3t5v]] - yPRTS subunit SEM1 + nuclear mRNA export proteins SAC3 and THP1<br />
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| **[[2z59]] - mPRTS subunit RPN13+ubiquitin<br />
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| **[[3txm]], [[3txn]] – PRTS subunit P42B – ''Drosophila melanogaster''
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| *Proteasome 26S particle
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| **[[3j47]], [[4cr2]], [[4cr3]], [[4cr4]], [[5wvi]], [[5mpc]] – yPRTS – Cryo EM<br />
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| **[[5wvk]] - yPRTS + ADP - Cryo EM<br />
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| **[[5mp9]], [[5mpa]], [[5mpd]], [[5mpe]] - yPRTS + ATP - Cryo EM<br />
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| **[[5mpb]] - yPRTS + AMPPNP - Cryo EM<br />
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| **[[4g4s]] – yPRTS + proteasome assembly chaperon 1 & 2<br />
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| **[[5a5b]] - yPRTS + UBP6 - Cryo EM<br />
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| **[[5l4g]], [[5gjr]], [[5ln3]], [[5t0c]], [[5t0g]], [[5t0h]], [[5t0i]], [[5t0j]] - hPRTS - Cryo EM<br />
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| **[[5m32]] - hPRTS + inhibitor - Cryo EM<br />
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| }}
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| == References == | | == References == |
| <references/> | | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |