View source for 1lnb


==A STRUCTURAL ANALYSIS OF METAL SUBSTITUTIONS IN THERMOLYSIN==
<StructureSection load='1lnb' size='340' side='right'caption='[[1lnb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lnb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/'bacillus_thermoproteolyticus' 'bacillus thermoproteolyticus']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LNB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LNB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=VAL:VALINE'>VAL</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lnb OCA], [http://pdbe.org/1lnb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lnb RCSB], [http://www.ebi.ac.uk/pdbsum/1lnb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lnb ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/THER_BACTH THER_BACTH]] Extracellular zinc metalloprotease. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ln/1lnb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lnb ConSurf].
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== Publication Abstract from PubMed ==
Native thermolysin binds a single catalytically essential zinc ion that is tetrahedrally coordinated by three protein ligands and a water molecule. During catalysis the zinc ligation is thought to change from fourfold to fivefold. Substitution of the active-site zinc with Cd2+, Mn2+, Fe2+, and Co2+ alters the catalytic activity (Holmquist B, Vallee BL, 1974, J Biol Chem 249:4601-4607). Excess zinc inhibits the enzyme. To investigate the structural basis of these changes in activity, we have determined the structures of a series of metal-substituted thermolysins at 1.7-1.9 A resolution. The structure of the Co(2+)-substituted enzyme is shown to be very similar to that of wild type except that two solvent molecules are liganded to the metal at positions that are thought to be occupied by the two oxygens of the hydrated scissile peptide in the transition state. Thus, the enhanced activity toward some substrates of the cobalt-relative to the zinc-substituted enzyme may be due to enhanced stabilization of the transition state. The ability of Zn2+ and Co2+ to accept tetrahedral coordination in the Michaelis complex, as well as fivefold coordination in the transition state, may also contribute to their effectiveness in catalysis. The Cd(2+)- and Mn(2+)-substituted thermolysins display conformational changes that disrupt the active site to varying degrees and could explain the associated reduction of activity. The conformational changes involve not only the essential catalytic residue, Glu 143, but also concerted side-chain rotations in the adjacent residues Met 120 and Leu 144. Some of these side-chain movements are similar to adjustments that have been observed previously in association with the "hinge-bending" motion that is presumed to occur during catalysis by the zinc endoproteases. In the presence of excess zinc, a second zinc ion is observed to bind at His 231 within 3.2 A of the zinc bound to native thermolysin, explaining the inhibitory effect.

Structural analysis of zinc substitutions in the active site of thermolysin.,Holland DR, Hausrath AC, Juers D, Matthews BW Protein Sci. 1995 Oct;4(10):1955-65. PMID:8535232<ref>PMID:8535232</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Thermolysin|Thermolysin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus thermoproteolyticus]]
[[Category: Large Structures]]
[[Category: Thermolysin]]
[[Category: Hausrath, A C]]
[[Category: Holland, D R]]
[[Category: Juers, D]]
[[Category: Matthews, B W]]