This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1mf4

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 02:32, 12 September 2015

Structure-based design of potent and selective inhibitors of phospholipase A2: Crystal structure of the complex formed between phosholipase A2 from Naja Naja sagittifera and a designed peptide inhibitor at 1.9 A resolution

Structural highlights

1mf4 is a 2 chain structure with sequence from Naja sagittifera. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1lff, 1ln8
Activity:	Phospholipase A(2), with EC number 3.1.1.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[PA2A3_NAJSG] PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Phospholipase A(2) (PLA(2)) (E. C. 3.1.1.4) is a common enzyme in the two-way cascade mechanism leading to the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to the membrane surface and hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before its cleavage. To regulate the production of proinflammatory compounds, a specific peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) for the group I PLA(2) enzymes has been designed and synthesized. PLA(2) was isolated from Indian cobra (Naja naja sagittifera) venom and purified to homogeneity. The binding studies indicated the K(i) value of 1.02 +/- 0.10 x 10(-8) M. The purified PLA(2) samples and the designed inhibitor VAFRS were cocrystallized. The crystal structure of the complex was determined and refined to 1.9 A resolution. The peptide binds to PLA(2) at the active site and fills the hydrophobic channel completely. However, its placement with respect to the channel is in the opposite direction as compared to those observed in group II PLA(2)'s. Furthermore, the predominant intermolecular interactions involve strong electrostatic interactions between the side chains of peptide Arg and Asp 49 of PLA(2) together with a number of van der Waals interactions with other residues. A good number of observed interactions between the peptide and the protein indicate the significance of a structure-based drug design approach. The novel factor in the present sequence of the peptide is related to the introduction of a positively charged residue at the C-terminal part of the peptide.

Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features.,Singh RK, Vikram P, Makker J, Jabeen T, Sharma S, Dey S, Kaur P, Srinivasan A, Singh TP Biochemistry. 2003 Oct 14;42(40):11701-6. PMID:14529280^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Singh RK, Vikram P, Makker J, Jabeen T, Sharma S, Dey S, Kaur P, Srinivasan A, Singh TP. Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features. Biochemistry. 2003 Oct 14;42(40):11701-6. PMID:14529280 doi:10.1021/bi035076x

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mf4"

@@ Line 6: / Line 6: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lff|1lff]], [[1ln8|1ln8]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mf4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1mf4 RCSB], [http://www.ebi.ac.uk/pdbsum/1mf4 PDBsum]</span></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=1mf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mf4 OCA], [http://pdbe.org/1mf4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mf4 RCSB], [http://www.ebi.ac.uk/pdbsum/1mf4 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PA23_NAJSG PA23_NAJSG]] PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
+[[http://www.uniprot.org/uniprot/PA2A3_NAJSG PA2A3_NAJSG]] PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1mf4" style="background-color:#fffaf0;"></div>
 ==See Also==

1mf4

From Proteopedia

Revision as of 02:32, 12 September 2015

Structure-based design of potent and selective inhibitors of phospholipase A2: Crystal structure of the complex formed between phosholipase A2 from Naja Naja sagittifera and a designed peptide inhibitor at 1.9 A resolution

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox