View source for 7bgu


==Mason-Pfizer Monkey Virus Protease mutant C7A/D26N/C106A in complex with peptidomimetic inhibitor==
<StructureSection load='7bgu' size='340' side='right'caption='[[7bgu]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bgu]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mason-Pfizer_monkey_virus Mason-Pfizer monkey virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.433&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0A1:O-METHYL-L-TYROSINE'>0A1</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PSA:3-HYDROXY-4-AMINO-5-PHENYLPENTANOIC+ACID'>PSA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7bgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgu OCA], [https://pdbe.org/7bgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgu RCSB], [https://www.ebi.ac.uk/pdbsum/7bgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POL_MPMV POL_MPMV] Matrix protein p10: Matrix protein.  Nucleocapsid protein p14: Nucleocapsid protein.  Capsid protein p27: Capsid protein.  Protease 17 kDa: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275]<ref>PMID:9636364</ref>   Protease 13 kDa: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275]<ref>PMID:9636364</ref>   G-patch peptide: Enhances the activity of the reverse transcriptase. May be part of the mature RT.<ref>PMID:22171253</ref>   Reverse transcriptase/ribonuclease H: RT is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to perfom a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perfom the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primers. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.[PROSITE-ProRule:PRU00405]  Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions.<ref>PMID:28458055</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mason-Pfizer monkey virus protease (PR) was crystallized in complex with two pepstatin-based inhibitors in P1 space group. In both crystal structures, the extended flap loops that lock the inhibitor/substrate over the active site, are visible in the electron density either completely or with only small gaps, providing the first observation of the conformation of the flap loops in dimeric complex form of this retropepsin. The H-bond network in the active site (with D26N mutation) differs from that reported for the P2(1) crystal structures and is similar to a rarely occurring system in HIV-1 PR.

Crystal structures of inhibitor complexes of M-PMV protease with visible flap loops.,Wosicki S, Kazmierczyk M, Gilski M, Zabranska H, Pichova I, Jaskolski M Protein Sci. 2021 Jun;30(6):1258-1263. doi: 10.1002/pro.4072. Epub 2021 Apr 8. PMID:33786913<ref>PMID:33786913</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bgu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mason-Pfizer monkey virus]]
[[Category: Synthetic construct]]
[[Category: Gilski M]]
[[Category: Jaskolski M]]
[[Category: Kazmierczyk M]]
[[Category: Pichova I]]
[[Category: Wosicki S]]
[[Category: Zabranska H]]