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| | <StructureSection load='6dr3' size='340' side='right'caption='[[6dr3]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6dr3' size='340' side='right'caption='[[6dr3]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dr3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DR3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DR3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dr3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DR3 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mhk|2mhk]], [[4p29|4p29]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.101Å</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=6dr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dr3 OCA], [http://pdbe.org/6dr3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dr3 RCSB], [http://www.ebi.ac.uk/pdbsum/6dr3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dr3 ProSAT]</span></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=6dr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dr3 OCA], [https://pdbe.org/6dr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dr3 RCSB], [https://www.ebi.ac.uk/pdbsum/6dr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dr3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LPOA_ECOLI LPOA_ECOLI]] Regulator of peptidoglycan synthesis that is essential for the function of penicillin-binding protein 1A (PBP1a). Stimulates transpeptidase activity of PBP1a in vitro.<ref>PMID:21183073</ref> <ref>PMID:21183074</ref> | + | [https://www.uniprot.org/uniprot/LPOA_ECOLI LPOA_ECOLI] Regulator of peptidoglycan synthesis that is essential for the function of penicillin-binding protein 1A (PBP1a). Stimulates transpeptidase activity of PBP1a in vitro.<ref>PMID:21183073</ref> <ref>PMID:21183074</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | In many Gram-negative bacteria, the peptidoglycan synthase PBP1A requires the outer membrane lipoprotein LpoA for constructing a functional peptidoglycan required for bacterial viability. Previously, we have shown that the C-terminal domain of Haemophilus influenzae LpoA (HiLpoA) has a highly conserved, putative substrate-binding cleft between two alpha/beta lobes. Here, we report a 2.0-A-resolution crystal structure of the HiLpoA N-terminal domain. Two subdomains contain tetratricopeptide-like motifs that form a concave groove, but their relative orientation differs by ~45 degrees from that observed in an NMR structure of the Escherichia coli LpoA N domain. We also determined three 2.0-2.8-A-resolution crystal structures containing four independent full-length HiLpoA molecules. In contrast to an elongated model previously suggested for E. coli LpoA, each HiLpoA formed a U-shaped structure with a different C-domain orientation. This resulted from both N-domain twisting and rotation of the C domain (up to 30 degrees ) at the end of the relatively immobile interdomain linker. Moreover, a previously predicted hinge between the lobes of the LpoA C domain exhibited variations of up to 12 degrees . Small-angle X-ray scattering (SAXS) data revealed excellent agreement with a model calculated by normal mode analysis (NMA) from one of the full-length HiLpoA molecules, but even better agreement with an ensemble of this molecule and two of the partially extended NMA-predicted models. The different LpoA structures helped explain how an outer membrane-anchored LpoA can either withdraw from or extend toward the inner membrane-bound PBP1A through peptidoglycan gaps and hence regulate the synthesis of peptidoglycan necessary for bacterial viability.
| + | The bacterial periplasmic protein LpoA is an outer membrane lipoprotein and an activator for the cross-linking activity of PBP1A, a bifunctional peptidoglycan synthase. Previous structures of the amino-terminal (N) domain of LpoA showed it to consist entirely of helices and loops, with at least four tetratricopeptide-like repeats. Although the previously determined orthorhombic crystal structure of the N domain of Haemophilus influenzae LpoA showed a typical curved structure with a concave groove, an NMR structure of the same domain from Escherichia coli was relatively flat. Here, a crystal structure of the N domain of E. coli LpoA was determined to a resolution of 2.1 A and was found to be more similar to the H. influenzae crystal structure than to the E. coli NMR structure. To provide a quantitative description for these comparisons, the various structures were superimposed pairwise by fitting the first half of each structure to its pairwise partner and then calculating the rotation axis that would optimally superimpose the second half. Differences in both the magnitude of the rotation and the direction of the rotation axis were observed between different pairs of structures. A 1.35 A resolution structure of a monoclinic crystal form of the N domain of H. influenzae LpoA was also determined. In this structure, the subdomains rotate 10 degrees relative to those in the original orthorhombic H. influenzae crystal structure to further narrow the groove between the subdomains. To accommodate this, a bound chloride ion (in place of sulfate) allowed the closer approach of a helix that forms one side of the groove. |
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| - | Structural analyses of the Haemophilus influenzae peptidoglycan synthase activator LpoA suggest multiple conformations in solution.,Sathiyamoorthy K, Vijayalakshmi J, Tirupati B, Fan L, Saper MA J Biol Chem. 2017 Sep 8. pii: jbc.M117.804997. doi: 10.1074/jbc.M117.804997. PMID:28887305<ref>PMID:28887305</ref>
| + | Crystal structures of the amino-terminal domain of LpoA from Escherichia coli and Haemophilus influenzae.,Kelley A, Vijayalakshmi J, Saper MA Acta Crystallogr F Struct Biol Commun. 2019 May 1;75(Pt 5):368-376. doi:, 10.1107/S2053230X19004011. Epub 2019 Apr 26. PMID:31045566<ref>PMID:31045566</ref> |
| | | | |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kelley, A C]] | + | [[Category: Kelley AC]] |
| - | [[Category: Saper, M A]] | + | [[Category: Saper MA]] |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: Tpr-like motifs outer membrane lipoprotein activator of pbp1a peptidoglycan]]
| + | |
| Structural highlights
Function
LPOA_ECOLI Regulator of peptidoglycan synthesis that is essential for the function of penicillin-binding protein 1A (PBP1a). Stimulates transpeptidase activity of PBP1a in vitro.[1] [2]
Publication Abstract from PubMed
The bacterial periplasmic protein LpoA is an outer membrane lipoprotein and an activator for the cross-linking activity of PBP1A, a bifunctional peptidoglycan synthase. Previous structures of the amino-terminal (N) domain of LpoA showed it to consist entirely of helices and loops, with at least four tetratricopeptide-like repeats. Although the previously determined orthorhombic crystal structure of the N domain of Haemophilus influenzae LpoA showed a typical curved structure with a concave groove, an NMR structure of the same domain from Escherichia coli was relatively flat. Here, a crystal structure of the N domain of E. coli LpoA was determined to a resolution of 2.1 A and was found to be more similar to the H. influenzae crystal structure than to the E. coli NMR structure. To provide a quantitative description for these comparisons, the various structures were superimposed pairwise by fitting the first half of each structure to its pairwise partner and then calculating the rotation axis that would optimally superimpose the second half. Differences in both the magnitude of the rotation and the direction of the rotation axis were observed between different pairs of structures. A 1.35 A resolution structure of a monoclinic crystal form of the N domain of H. influenzae LpoA was also determined. In this structure, the subdomains rotate 10 degrees relative to those in the original orthorhombic H. influenzae crystal structure to further narrow the groove between the subdomains. To accommodate this, a bound chloride ion (in place of sulfate) allowed the closer approach of a helix that forms one side of the groove.
Crystal structures of the amino-terminal domain of LpoA from Escherichia coli and Haemophilus influenzae.,Kelley A, Vijayalakshmi J, Saper MA Acta Crystallogr F Struct Biol Commun. 2019 May 1;75(Pt 5):368-376. doi:, 10.1107/S2053230X19004011. Epub 2019 Apr 26. PMID:31045566[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Typas A, Banzhaf M, van den Berg van Saparoea B, Verheul J, Biboy J, Nichols RJ, Zietek M, Beilharz K, Kannenberg K, von Rechenberg M, Breukink E, den Blaauwen T, Gross CA, Vollmer W. Regulation of peptidoglycan synthesis by outer-membrane proteins. Cell. 2010 Dec 23;143(7):1097-109. doi: 10.1016/j.cell.2010.11.038. PMID:21183073 doi:http://dx.doi.org/10.1016/j.cell.2010.11.038
- ↑ Paradis-Bleau C, Markovski M, Uehara T, Lupoli TJ, Walker S, Kahne DE, Bernhardt TG. Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases. Cell. 2010 Dec 23;143(7):1110-20. doi: 10.1016/j.cell.2010.11.037. PMID:21183074 doi:http://dx.doi.org/10.1016/j.cell.2010.11.037
- ↑ Kelley A, Vijayalakshmi J, Saper MA. Crystal structures of the amino-terminal domain of LpoA from Escherichia coli and Haemophilus influenzae. Acta Crystallogr F Struct Biol Commun. 2019 May 1;75(Pt 5):368-376. doi:, 10.1107/S2053230X19004011. Epub 2019 Apr 26. PMID:31045566 doi:http://dx.doi.org/10.1107/S2053230X19004011
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