4tmn: Difference between revisions

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-{{Seed}}
-[[Image:4tmn.png|left|200px]]
-<!--
+==SLOW-AND FAST-BINDING INHIBITORS OF THERMOLYSIN DISPLAY DIFFERENT MODES OF BINDING. CRYSTALLOGRAPHIC ANALYSIS OF EXTENDED PHOSPHONAMIDATE TRANSITION-STATE ANALOGUES==
-The line below this paragraph, containing "STRUCTURE_4tmn", creates the "Structure Box" on the page.
+<StructureSection load='4tmn' size='340' side='right'caption='[[4tmn]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[4tmn]] 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=4TMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TMN FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0PK:N-[(S)-[(1R)-1-{[(BENZYLOXY)CARBONYL]AMINO}-2-PHENYLETHYL](HYDROXY)PHOSPHORYL]-L-LEUCYL-L-ALANINE'>0PK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_4tmn|  PDB=4tmn  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tmn OCA], [https://pdbe.org/4tmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tmn RCSB], [https://www.ebi.ac.uk/pdbsum/4tmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tmn 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/tm/4tmn_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=4tmn ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The modes of binding to thermolysin of two phosphonamidate peptide inhibitors, carbobenzoxy-GlyP-L-Leu-L-Leu (ZGPLL) and carbobenzoxy-L-PheP-L-Leu-L-Ala (ZFPLA), have been determined by X-ray crystallography and refined at high resolution to crystallographic R-values of 17.7% and 17.0%, respectively. (GlyP is used to indicate that the trigonal carbon of the peptide linkage is replaced by the tetrahedral phosphorus of a phosphonamidate group.). These inhibitors were designed to be structural analogues of the presumed catalytic transition state and are potent inhibitors of thermolysin (ZGPLL, Ki = 9.1 nM; ZFPLA, Ki = 0.068 nM) [Bartlett, P. A., &amp; Marlowe, C. K. (1987) Biochemistry (following paper in this issue)]. ZFPLA binds to thermolysin in the manner expected for the transition state and, for the first time, provides direct support for the presumed mode of binding of extended substrates in the S2 subsite. The mode of binding of ZFPLA displays all the interactions that are presumed to stabilize the transition state and supports the postulated mechanism of catalysis [Hangauer, D. G., Monzingo, A. F., &amp; Matthews, B. W. (1984) Biochemistry 23, 5730-5741]. The two oxygens of the phosphonamidate moiety are liganded to the zinc to give overall pentacoordination of the metal. For the second inhibitor the situation is different. Although both ZFPLA and ZGPLL have similar modes of binding in the S1' and S2' subsites, the configurations of the carbobenzoxy-Phe and carbobenzoxy-Gly moieties are different. For ZFPLA the carbonyl group of the carbobenzoxy group is hydrogen bonded directly to the enzyme, whereas in ZGPLL the carbonyl group is rotated 117 degrees, and there is a water molecule interposed between the inhibitor and the enzyme. For ZGPLL only one of the phosphonamidate oxygens is liganded to the zinc. Correlated with the change in inhibitor-zinc ligation from monodentate in ZGPLL to bidentate in ZFPLA there is an increase in the phosphorus-nitrogen bond length of about 0.25 A, strongly suggesting that the phosphonamide nitrogen in ZFPLA is cationic, analogous to the doubly protonated nitrogen of the transition state. The observation that the nitrogen of ZFPLA appears to donate two hydrogen bonds to the protein also indicates that it is cationic. The different configurations adopted by the respective inhibitors are correlated with large differences in their kinetics of binding [Bartlett, P. A., &amp; Marlowe, C. K. (1987) Biochemistry (following paper in this issue)]. These differences in kinetics are not associated with any significant conformational change on the part of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
-===SLOW-AND FAST-BINDING INHIBITORS OF THERMOLYSIN DISPLAY DIFFERENT MODES OF BINDING. CRYSTALLOGRAPHIC ANALYSIS OF EXTENDED PHOSPHONAMIDATE TRANSITION-STATE ANALOGUES===
+Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues.,Holden HM, Tronrud DE, Monzingo AF, Weaver LH, Matthews BW Biochemistry. 1987 Dec 29;26(26):8542-53. PMID:3442675<ref>PMID:3442675</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4tmn" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_3442675}}, adds the Publication Abstract to the page
+*[[Thermolysin 3D structures|Thermolysin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 3442675 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_3442675}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Bacillus thermoproteolyticus]]
-TMN is a 2 chains structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TMN OCA].
+[[Category: Large Structures]]
+[[Category: Holden HM]]
-==Reference==
+[[Category: Matthews BW]]
-<ref group="xtra">PMID:3442675</ref><references group="xtra"/>
+[[Category: Monzingo AF]]
-[[Category: Thermolysin]]
+[[Category: Tronrud DE]]
-[[Category: Holden, H M.]]
+[[Category: Weaver LH]]
-[[Category: Matthews, B W.]]
-[[Category: Monzingo, A F.]]
-[[Category: Tronrud, D E.]]
-[[Category: Weaver, L H.]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 00:33:52 2009''