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New page: left|200px<br /><applet load="1tlp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tlp, resolution 2.3Å" /> '''CRYSTALLOGRAPHIC STRU...
 
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[[Image:1tlp.gif|left|200px]]<br /><applet load="1tlp" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1tlp, resolution 2.3&Aring;" />
'''CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN'''<br />


==Overview==
==CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN==
The mode of binding to thermolysin of the unsubstituted phosphoramidate, inhibitor N-phosphoryl-L-leucinamide (P-Leu-NH2) has been determined, crystallographically and refined at high resolution (R = 17.9% to 0.16-nm, resolution). The mode of binding of the naturally occurring thermolysin, inhibitor phosphoramidon reported previously [Weaver, L. H., Kester, W. R., and Matthews, B. W. (1977) J. Mol. Biol. 114, 119-132] has also been, confirmed by crystallographic refinement (R = 17.4% to 0.23-nm, resolution). Phosphoramidon binds to the enzyme with a single oxygen of, the phosphoramidate moiety as a zinc ligand. Together with three ligands, to the metal from the protein the resultant complex has approximately, tetrahedral geometry. However, in the case of P-Leu-NH2, two of the, phosphoramidate oxygens interact with the zinc to form a complex that, tends towards pentacoordinate. In this respect, P-Leu-NH2 appears to be a, better transition-state analog than is phosphoramidon. In addition, the, phosphorus-nitrogen bond length in P-Leu-NH2 is 0.18 nm, suggesting that, the nitrogen is protonated whereas the same bond in phosphoramidon is much, shorter (0.15 nm) suggesting that the nitrogen does not carry a charge. In, phosphoramidon the distance from the phosphoramide nitrogen to Glu-143 is, 0.39 nm whereas in P-Leu-NH2 this distance decreases to 0.34 nm. Taken, together, these observations provide additional evidence in support of the, participation of pentacoordinate intermediates in the mechanism of action, of thermolysin [Holmes, M. A. and Matthews, B. W. (1981) Biochemistry 20, 6912-6920] and the role of Glu-143 in first promoting the attack of a, water molecule on the carbonyl carbon of the scissile bond and, subsequently acting as a 'proton shuttle' to transfer the proton to the, leaving nitrogen [Monzingo, A. F. and Matthews, B. W. (1984) Biochemistry, 23, 5724-5729; Hangauer, D. G., Monzingo, A. F. and Matthews, B. W. (1984), Biochemistry 23, 5730-5741].
<StructureSection load='1tlp' size='340' side='right'caption='[[1tlp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tlp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TLP 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]] 2.3&#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=RDF:N-ALPHA-L-RHAMNOPYRANOSYLOXY(HYDROXYPHOSPHINYL)-L-LEUCYL-L-TRYPTOPHAN'>RDF</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=1tlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tlp OCA], [https://pdbe.org/1tlp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tlp RCSB], [https://www.ebi.ac.uk/pdbsum/1tlp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tlp ProSAT]</span></td></tr>
</table>
== Function ==
[https://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/tl/1tlp_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=1tlp ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1TLP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with RHA, CA and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TLP OCA].
*[[Thermolysin 3D structures|Thermolysin 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin., Tronrud DE, Monzingo AF, Matthews BW, Eur J Biochem. 1986 Jun 2;157(2):261-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=3709536 3709536]
[[Category: Bacillus thermoproteolyticus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Thermolysin]]
[[Category: Matthews BW]]
[[Category: Matthews, B.W.]]
[[Category: Monzingo AF]]
[[Category: Monzingo, A.F.]]
[[Category: Tronrud DE]]
[[Category: Tronrud, D.E.]]
[[Category: CA]]
[[Category: RHA]]
[[Category: ZN]]
[[Category: hydrolase (metalloproteinase)]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:23:12 2007''

Latest revision as of 13:30, 13 March 2024

CRYSTALLOGRAPHIC STRUCTURAL ANALYSIS OF PHOSPHORAMIDATES AS INHIBITORS AND TRANSITION-STATE ANALOGS OF THERMOLYSIN

1tlp, resolution 2.30Å

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