View source for 3vv2


==Crystal structure of complex form between S324A-subtilisin and mutant Tkpro==
<StructureSection load='3vv2' size='340' side='right'caption='[[3vv2]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vv2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermococcus_kodakarensis_KOD1 Thermococcus kodakarensis KOD1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VV2 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]] 1.83&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=3vv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vv2 OCA], [https://pdbe.org/3vv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vv2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vv2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TKSU_THEKO TKSU_THEKO] Has a broad substrate specificity with a slight preference to large hydrophobic amino acid residues at the P1 position.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tk-subtilisin, a subtilisin homologue (Gly70-Gly398) from Thermococcus kodakarensis, is matured from its precursor, Pro-Tk-subtilisin [Tk-subtilisin in a pro form (Gly1-Gly398)], by autoprocessing and degradation of propeptide [Tk-propeptide, a propeptide of Tk-subtilisin (Gly1-Leu69)]. The scissile peptide bond between Leu69 and Gly70 of Pro-Tk-subtilisin is first self-cleaved to produce an inactive Tk-propeptide:Tk-subtilisin complex, in which the C-terminal region of Tk-propeptide binds to the active-site cleft of Tk-subtilisin. Tk-propeptide is then dissociated from Tk-subtilisin and degraded by Tk-subtilisin to release active Tk-subtilisin. To examine whether the mutation of Leu69 to Pro, which is the most unfavourable residue in the P1 position for subtilisins, affects the maturation of Pro-Tk-subtilisin, the Pro-Tk-subtilisin and Tk-propeptide derivatives with this mutation (Pro-L69P and L69P-propeptide) were constructed and characterized. Pro-L69P was autoprocessed more slowly than Pro-Tk-subtilisin. Nevertheless, it matured to Tk-subtilisin more rapidly than Pro-Tk-subtilisin because L69P-propeptide was degraded by Tk-subtilisin more rapidly than Tk-propeptide. The chaperone function and stability of L69P-propeptide were comparable to those of Tk-propeptide, whereas the inhibitory potency and binding ability of L69P-propeptide were considerably reduced compared to those of Tk-propeptide. The crystal structure of the complex between L69P-propeptide and S324A-subtilisin (i.e. a protease activity-defective mutant) revealed that the C-terminal region of L69P-propeptide does not well fit into the substrate binding pockets of Tk-subtilisin (S1-S4 subsites) as a result of a conformational change caused by the mutation. These results suggest that the Leu--&gt;Pro mutation accelerates the maturation of Pro-Tk-subtilisin by reducing the binding ability of Tk-propeptide to Tk-subtilisin. DATABASE: The coordinates and structure factors have been deposited in the RCSB Protein Data Bank under ID code: 3VV2. STRUCTURED DIGITAL ABSTRACT: Pro-Tk-subtilisin and Pro-Tk-subtilisin cleave by enzymatic study (View interaction) L69P-propeptide and S324A-subtilisin bind by x-ray crystallography (View interaction) Tk-propeptide binds to S324A-subtilisin by surface plasmon resonance (View interaction).

Accelerated maturation of Tk-subtilisin by a Leu--&gt;Promutation at the C-terminus of the propeptide, which reduces the binding of the propeptide to Tk-subtilisin.,Uehara R, Ueda Y, You DJ, Koga Y, Kanaya S FEBS J. 2013 Feb;280(4):994-1006. doi: 10.1111/febs.12091. Epub 2013 Jan 11. PMID:23237738<ref>PMID:23237738</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vv2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Subtilisin 3D structures|Subtilisin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermococcus kodakarensis KOD1]]
[[Category: Kanaya S]]
[[Category: Koga Y]]
[[Category: Takano K]]
[[Category: Ueda Y]]
[[Category: Uehara R]]
[[Category: You DJ]]