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| | <StructureSection load='5vet' size='340' side='right'caption='[[5vet]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5vet' size='340' side='right'caption='[[5vet]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vet]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russellii_pulchella Daboia russellii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VET FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vet]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russelii_pulchella Daboia russelii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VET FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jq8|1jq8]]</div></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]] 2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </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=5vet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vet OCA], [https://pdbe.org/5vet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vet RCSB], [https://www.ebi.ac.uk/pdbsum/5vet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vet 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=5vet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vet OCA], [https://pdbe.org/5vet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vet RCSB], [https://www.ebi.ac.uk/pdbsum/5vet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vet ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PA2B8_DABRR PA2B8_DABRR] Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:18062812</ref> <ref>PMID:2115497</ref> <ref>PMID:8835338</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | Phospholipase A(2) (EC 3.1.1.4) is a key enzyme of the cascade mechanism involved in the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to membrane surfaces and the hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before cleavage. In order to regulate the production of proinflammatory compounds, a specific peptide inhibitor of PLA(2), Leu-Ala-Ile-Tyr-Ser, has been designed. Phospholipase A(2) from Daboia russelli pulchella (DPLA(2)) and peptide Leu-Ala-Ile-Tyr-Ser (LAIYS) have been co-crystallized. The structure of the complex has been determined and refined to 2.0 A resolution. The structure contains two crystallographically independent molecules of DPLA(2), with one molecule of peptide specifically bound to one of them. The overall conformations of the two molecules are essentially similar except in three regions; namely, the calcium-binding loop including Trp31 (residues 25-34), the beta-wing consisting of two antiparallel beta-strands (residues 74-85) and the C-terminal region (residues 119-133). Of these, the most striking difference pertains to the orientation of Trp31 in the two molecules. The conformation of Trp31 in molecule A was suitable to allow the binding of peptide LAIYS, while that in molecule B prevented the entry of the ligand into the hydrophobic channel. The structure of the complex clearly showed that the OH group of Tyr of the inhibitor formed hydrogen bonds with both His48 N(delta1) and Asp49 O(delta1), while O(gamma)H of Ser was involved in a hydrogen bond with Trp31. Other peptide backbone atoms interact with protein through water molecules, while Leu, Ala and Ile form strong hydrophobic interactions with the residues of the hydrophobic channel.
| + | The massive technical and computational progress of biomolecular crystallography has generated some adverse side effects. Most crystal structure models, produced by crystallographers or well-trained structural biologists, constitute useful sources of information, but occasional extreme outliers remind us that the process of structure determination is not fail-safe. The occurrence of severe errors or gross misinterpretations raises fundamental questions: Why do such aberrations emerge in the first place? How did they evade the sophisticated validation procedures which often produce clear and dire warnings, and why were severe errors not noticed by the depositors themselves, their supervisors, referees, and editors? Once detected, what can be done to either correct, improve, or eliminate such models? How do incorrect models affect the underlying claims or biomedical hypotheses they were intended, but failed, to support? What is the long-range effect of the propagation of such errors? And finally, what mechanisms can be envisioned to restore the validity of the scientific record and, if necessary, retract publications that are clearly invalidated by the lack of experimental evidence? We suggest that cognitive bias and flawed epistemology are likely at the root of the problem. By using examples from the published literature and from public repositories such as the Protein Data Bank, we provide case summaries to guide correction or improvement of structural models. When strong claims are unsustainable because of a deficient crystallographic model, removal of such a model and even retraction of the affected publication are necessary to restore the integrity of the scientific record. This article is protected by copyright. All rights reserved. |
| | | | |
| - | Design of specific peptide inhibitors of phospholipase A2: structure of a complex formed between Russell's viper phospholipase A2 and a designed peptide Leu-Ala-Ile-Tyr-Ser (LAIYS).,Chandra V, Jasti J, Kaur P, Dey S, Srinivasan A, Betzel Ch, Singh TP Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 2):1813-9. Epub, 2002 Sep 28. PMID:12351825<ref>PMID:12351825</ref>
| + | Detect, Correct, Retract: How to manage incorrect structural models.,Wlodawer A, Dauter Z, Porebski PJ, Minor W, Stanfield R, Jaskolski M, Pozharski E, Weichenberger CX, Rupp B FEBS J. 2017 Nov 7. doi: 10.1111/febs.14320. PMID:29113027<ref>PMID:29113027</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: Daboia russellii pulchella]] | + | [[Category: Daboia russelii pulchella]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dauter, Z]] | + | [[Category: Dauter Z]] |
| - | [[Category: Jaskolski, M]] | + | [[Category: Jaskolski M]] |
| - | [[Category: Minor, W]] | + | [[Category: Minor W]] |
| - | [[Category: Porebski, P]] | + | [[Category: Porebski P]] |
| - | [[Category: Pozharski, E]] | + | [[Category: Pozharski E]] |
| - | [[Category: Rupp, B]] | + | [[Category: Rupp B]] |
| - | [[Category: Stanfield, R]] | + | [[Category: Stanfield R]] |
| - | [[Category: Weichenberger, C X]] | + | [[Category: Weichenberger CX]] |
| - | [[Category: Wlodawer, A]] | + | [[Category: Wlodawer A]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phospholipase a2]]
| + | |
| - | [[Category: Re-refinement]]
| + | |
| Structural highlights
Function
PA2B8_DABRR Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.[1] [2] [3]
Publication Abstract from PubMed
The massive technical and computational progress of biomolecular crystallography has generated some adverse side effects. Most crystal structure models, produced by crystallographers or well-trained structural biologists, constitute useful sources of information, but occasional extreme outliers remind us that the process of structure determination is not fail-safe. The occurrence of severe errors or gross misinterpretations raises fundamental questions: Why do such aberrations emerge in the first place? How did they evade the sophisticated validation procedures which often produce clear and dire warnings, and why were severe errors not noticed by the depositors themselves, their supervisors, referees, and editors? Once detected, what can be done to either correct, improve, or eliminate such models? How do incorrect models affect the underlying claims or biomedical hypotheses they were intended, but failed, to support? What is the long-range effect of the propagation of such errors? And finally, what mechanisms can be envisioned to restore the validity of the scientific record and, if necessary, retract publications that are clearly invalidated by the lack of experimental evidence? We suggest that cognitive bias and flawed epistemology are likely at the root of the problem. By using examples from the published literature and from public repositories such as the Protein Data Bank, we provide case summaries to guide correction or improvement of structural models. When strong claims are unsustainable because of a deficient crystallographic model, removal of such a model and even retraction of the affected publication are necessary to restore the integrity of the scientific record. This article is protected by copyright. All rights reserved.
Detect, Correct, Retract: How to manage incorrect structural models.,Wlodawer A, Dauter Z, Porebski PJ, Minor W, Stanfield R, Jaskolski M, Pozharski E, Weichenberger CX, Rupp B FEBS J. 2017 Nov 7. doi: 10.1111/febs.14320. PMID:29113027[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Faure G, Gowda VT, Maroun RC. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics. BMC Struct Biol. 2007 Dec 6;7:82. PMID:18062812 doi:http://dx.doi.org/10.1186/1472-6807-7-82
- ↑ Kasturi S, Rudrammaji LM, Gowda TV. Antibodies to a phospholipase A2 from Vipera russelli selectively neutralize venom neurotoxicity. Immunology. 1990 Jun;70(2):175-80. PMID:2115497
- ↑ Tsai IH, Lu PJ, Su JC. Two types of Russell's viper revealed by variation in phospholipases A2 from venom of the subspecies. Toxicon. 1996 Jan;34(1):99-109. PMID:8835338
- ↑ Wlodawer A, Dauter Z, Porebski PJ, Minor W, Stanfield R, Jaskolski M, Pozharski E, Weichenberger CX, Rupp B. Detect, Correct, Retract: How to manage incorrect structural models. FEBS J. 2017 Nov 7. doi: 10.1111/febs.14320. PMID:29113027 doi:http://dx.doi.org/10.1111/febs.14320
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