4m6r: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4m6r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M6R FirstGlance]. <br>
<table><tr><td colspan='2'>[[4m6r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M6R FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4m6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m6r OCA], [https://pdbe.org/4m6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m6r RCSB], [https://www.ebi.ac.uk/pdbsum/4m6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m6r ProSAT]</span></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=4m6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m6r OCA], [https://pdbe.org/4m6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m6r RCSB], [https://www.ebi.ac.uk/pdbsum/4m6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m6r ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/MTNB_HUMAN MTNB_HUMAN] Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death.<ref>PMID:15262985</ref> <ref>PMID:23285211</ref> <ref>PMID:22837397</ref>  
[https://www.uniprot.org/uniprot/MTNB_HUMAN MTNB_HUMAN] Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death.<ref>PMID:15262985</ref> <ref>PMID:23285211</ref> <ref>PMID:22837397</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
APIP, Apaf-1 interacting protein, has been known to inhibit two main types of programmed cell death, apoptosis and pyroptosis, and was recently found to be associated with cancers and inflammatory diseases. Distinct from its inhibitory role in cell death, APIP was also shown to act as a 5-methylthioribulose-1-phosphate dehydratase, or MtnB, in the methionine salvage pathway. Here we report the structural and enzymatic characterization of human APIP as an MtnB enzyme with a Km of 9.32 muM and a Vmax of 1.39 mumol min(-1) mg(-1). The crystal structure was determined at 2.0-A resolution, revealing an overall fold similar to members of the zinc-dependent class II aldolase family. APIP/MtnB exists as a tetramer in solution and exhibits an assembly with C4 symmetry in the crystal lattice. The pocket-shaped active site is located at the end of a long cleft between two adjacent subunits. We propose an enzymatic reaction mechanism involving Glu139* as a catalytic acid/base, as supported by enzymatic assay, substrate-docking study, and sequence conservation analysis. We explored the relationship between two distinct functions of APIP/MtnB, cell death inhibition, and methionine salvage, by measuring the ability of enzymatic mutants to inhibit cell death, and determined that APIP/MtnB functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis induced by either hypoxia or etoposide, but dependently for caspase-1-induced pyroptosis. Our results establish the structural and biochemical groundwork for future mechanistic studies of the role of APIP/MtnB in modulating cell death and inflammation and in the development of related diseases.
Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme.,Kang W, Hong SH, Lee HM, Kim NY, Lim YC, Le le TM, Lim B, Kim HC, Kim TY, Ashida H, Yokota A, Hah SS, Chun KH, Jung YK, Yang JK Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):E54-61. doi: 10.1073/pnas.1308768111., Epub 2013 Dec 23. PMID:24367089<ref>PMID:24367089</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4m6r" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 08:55, 20 March 2024

Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme

4m6r, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=4m6r&oldid=4105257"