View source for 4njp


==Proteolysis inside the membrane is a rate-governed reaction not Driven by substrate affinity==
<StructureSection load='4njp' size='340' side='right'caption='[[4njp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4njp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NJP 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]] 2.4&#8491;</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=4njp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njp OCA], [https://pdbe.org/4njp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4njp RCSB], [https://www.ebi.ac.uk/pdbsum/4njp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4njp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLPG_ECOLI GLPG_ECOLI] Rhomboid-type serine protease that catalyzes intramembrane proteolysis.<ref>PMID:17099694</ref> <ref>PMID:16216077</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enzymatic cleavage of transmembrane anchors to release proteins from the membrane controls diverse signaling pathways and is implicated in more than a dozen diseases. How catalysis works within the viscous, water-excluding, two-dimensional membrane is unknown. We developed an inducible reconstitution system to interrogate rhomboid proteolysis quantitatively within the membrane in real time. Remarkably, rhomboid proteases displayed no physiological affinity for substrates (Kd approximately 190 muM/0.1 mol%). Instead, approximately 10,000-fold differences in proteolytic efficiency with substrate mutants and diverse rhomboid proteases were reflected in kcat values alone. Analysis of gate-open mutant and solvent isotope effects revealed that substrate gating, not hydrolysis, is rate limiting. Ultimately, a single proteolytic event within the membrane normally takes minutes. Rhomboid intramembrane proteolysis is thus a slow, kinetically controlled reaction not driven by transmembrane protein-protein affinity. These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications.

Proteolysis inside the Membrane Is a Rate-Governed Reaction Not Driven by Substrate Affinity.,Dickey SW, Baker RP, Cho S, Urban S Cell. 2013 Dec 5;155(6):1270-81. doi: 10.1016/j.cell.2013.10.053. PMID:24315097<ref>PMID:24315097</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4njp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Rhomboid protease|Rhomboid protease]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Baker RP]]
[[Category: Cho S]]
[[Category: Dickey SW]]
[[Category: Urban S]]