1o75: Difference between revisions
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==Tp47, the 47-Kilodalton Lipoprotein of Treponema pallidum== | |||
<StructureSection load='1o75' size='340' side='right'caption='[[1o75]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
| | <table><tr><td colspan='2'>[[1o75]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Treponema_pallidum Treponema pallidum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O75 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O75 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PDX:2,3-DI-O-SULFO-ALPHA-D-GLUCOPYRANOSE'>PDX</scene>, <scene name='pdbligand=XE:XENON'>XE</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=1o75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o75 OCA], [https://pdbe.org/1o75 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o75 RCSB], [https://www.ebi.ac.uk/pdbsum/1o75 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o75 ProSAT]</span></td></tr> | |||
</table> | |||
''' | == Function == | ||
[https://www.uniprot.org/uniprot/TA47_TREPA TA47_TREPA] This antigen is a pathogen-specific membrane immunogen. Most abundant of the membrane lipoproteins, only found so far in pathogenic treponemes, suggesting that it is an important structural moiety in the cell envelope of virulent treponemal subspecies. | |||
<div style="background-color:#fffaf0;"> | |||
== | == Publication Abstract from PubMed == | ||
Syphilis is a complex sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum. T. pallidum has remained exquisitely sensitive to penicillin, but the mode of action and lethal targets for beta-lactams are still unknown. We previously identified the T. pallidum 47-kDa lipoprotein (Tp47) as a penicillin-binding protein (PBP). Tp47 contains three hypothetical consensus motifs (SVTK, TEN, and KTG) that typically form the active center of other PBPs. Yet, in this study, mutations of key amino acids within these motifs failed to abolish the penicillin binding activity of Tp47. The crystal structure of Tp47 at a resolution of 1.95 A revealed a fold different from any other known PBP; Tp47 is predominantly beta-sheet, in contrast to the alpha/beta-fold common to other PBPs. It comprises four distinct domains: two complex beta-sheet-containing N-terminal domains and two C-terminal domains that adopt immunoglobulin-like folds. The three hypothetical PBP signature motifs do not come together to form a typical PBP active site. Furthermore, Tp47 is unusual in that it displays beta-lactamase activity (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that hindered attempts to identify the active site in Tp47 by co-crystallization and mass spectrometric techniques. Taken together, Tp47 does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP. | Syphilis is a complex sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum. T. pallidum has remained exquisitely sensitive to penicillin, but the mode of action and lethal targets for beta-lactams are still unknown. We previously identified the T. pallidum 47-kDa lipoprotein (Tp47) as a penicillin-binding protein (PBP). Tp47 contains three hypothetical consensus motifs (SVTK, TEN, and KTG) that typically form the active center of other PBPs. Yet, in this study, mutations of key amino acids within these motifs failed to abolish the penicillin binding activity of Tp47. The crystal structure of Tp47 at a resolution of 1.95 A revealed a fold different from any other known PBP; Tp47 is predominantly beta-sheet, in contrast to the alpha/beta-fold common to other PBPs. It comprises four distinct domains: two complex beta-sheet-containing N-terminal domains and two C-terminal domains that adopt immunoglobulin-like folds. The three hypothetical PBP signature motifs do not come together to form a typical PBP active site. Furthermore, Tp47 is unusual in that it displays beta-lactamase activity (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that hindered attempts to identify the active site in Tp47 by co-crystallization and mass spectrometric techniques. Taken together, Tp47 does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP. | ||
Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals a novel penicillin-binding protein.,Deka RK, Machius M, Norgard MV, Tomchick DR J Biol Chem. 2002 Nov 1;277(44):41857-64. Epub 2002 Aug 24. PMID:12196546<ref>PMID:12196546</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1o75" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Treponema pallidum]] | [[Category: Treponema pallidum]] | ||
[[Category: Deka | [[Category: Deka RK]] | ||
[[Category: Machius | [[Category: Machius M]] | ||
[[Category: Norgard | [[Category: Norgard MV]] | ||
[[Category: Tomchick | [[Category: Tomchick DR]] | ||
Latest revision as of 11:57, 9 May 2024
Tp47, the 47-Kilodalton Lipoprotein of Treponema pallidumTp47, the 47-Kilodalton Lipoprotein of Treponema pallidum
Structural highlights
FunctionTA47_TREPA This antigen is a pathogen-specific membrane immunogen. Most abundant of the membrane lipoproteins, only found so far in pathogenic treponemes, suggesting that it is an important structural moiety in the cell envelope of virulent treponemal subspecies. Publication Abstract from PubMedSyphilis is a complex sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum. T. pallidum has remained exquisitely sensitive to penicillin, but the mode of action and lethal targets for beta-lactams are still unknown. We previously identified the T. pallidum 47-kDa lipoprotein (Tp47) as a penicillin-binding protein (PBP). Tp47 contains three hypothetical consensus motifs (SVTK, TEN, and KTG) that typically form the active center of other PBPs. Yet, in this study, mutations of key amino acids within these motifs failed to abolish the penicillin binding activity of Tp47. The crystal structure of Tp47 at a resolution of 1.95 A revealed a fold different from any other known PBP; Tp47 is predominantly beta-sheet, in contrast to the alpha/beta-fold common to other PBPs. It comprises four distinct domains: two complex beta-sheet-containing N-terminal domains and two C-terminal domains that adopt immunoglobulin-like folds. The three hypothetical PBP signature motifs do not come together to form a typical PBP active site. Furthermore, Tp47 is unusual in that it displays beta-lactamase activity (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that hindered attempts to identify the active site in Tp47 by co-crystallization and mass spectrometric techniques. Taken together, Tp47 does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP. Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals a novel penicillin-binding protein.,Deka RK, Machius M, Norgard MV, Tomchick DR J Biol Chem. 2002 Nov 1;277(44):41857-64. Epub 2002 Aug 24. PMID:12196546[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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