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.


1nma

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1nma" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nma, resolution 3.0&Aring;" /> '''N9 NEURAMINIDASE COM...)
Current revision (08:51, 10 April 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1nma.gif|left|200px]]<br />
 
-
<applet load="1nma" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1nma, resolution 3.0&Aring;" />
 
-
'''N9 NEURAMINIDASE COMPLEXES WITH ANTIBODIES NC41 AND NC10: EMPIRICAL FREE-ENERGY CALCULATIONS CAPTURE SPECIFICITY TRENDS OBSERVED WITH MUTANT BINDING DATA'''<br />
 
-
==Overview==
+
==N9 NEURAMINIDASE COMPLEXES WITH ANTIBODIES NC41 AND NC10: EMPIRICAL FREE-ENERGY CALCULATIONS CAPTURE SPECIFICITY TRENDS OBSERVED WITH MUTANT BINDING DATA==
-
X-ray crystallographic coordinates of influenza virus N9 neuraminidase, complexed with monoclonal antibodies NC41 and NC10 [Tulip et al. (1992) J., Mol. Biol. 227, 122-148] served as a starting point for calculations aimed, at estimating free energy changes (delta G) of complex formation between, the two antibodies and the neuraminidase. Using an empirical function, incorporating hydrophobic, electrostatic, and conformational entropy, effects, we estimated contributions individual neuraminidase residues make, to complex formation (delta G(residue)) and compared the calculated values, to experimentally measured differences in antibody binding between the, wild-type and mutated neuraminidases [Nuss et al. (1993) Proteins 15, 121-132; calculations done without prior knowledge of the experimental, data]. A good correspondence was found between the calculated delta, G(residue) values and the mutant binding data in that side chains with, large calculated delta G contributions (delta G(residue) &lt; -1 kcal/mol), lie at sites of mutation which cause a marked reduction in antibody, binding, and side chains for which delta G(residue) &gt; -1 kcal/mol are, sites at which a mutation does not have a marked effect on binding., Because most of the delta G(residue) &lt; -1 kcal/mol side chains also make, hydrogen bonds/salt bridges with the antibody, the correspondence of the, effect of antibody binding with these electrostatic interactions (18 out, of 27 for NC41 and, tentatively, 5 out of 7 for NC10) is about as good as, that with predicted energetic residues. All the delta G(residue) &lt; -1, kcal/mol neuraminidase side chains cluster around the most protruding, surface regions and are thus spread over different epitope segments., Surprisingly, different residues were found to make the most critical, contributions to the NC41 and NC10 complex stabilities despite the fact, that the NC41 and NC10 antigenic epitopes overlap, having approximately, 70% of surface residues in common. It is thus possible, for two different, antibodies, to recognize the same protein surface in strikingly different, ways. As only a fraction of the neuraminidase residues appear to make, large contributions to antibody binding, the results also support the, hypothesis of a "functional" epitope in antigen-antibody interactions., Positive trends between both backbone rigidity and residue accessibility, in the complexed state, and contributions of these residues to binding, were also observed for the NC41 complex.
+
<StructureSection load='1nma' size='340' side='right'caption='[[1nma]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1nma]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NMA 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]] 3&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1nma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nma OCA], [https://pdbe.org/1nma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nma RCSB], [https://www.ebi.ac.uk/pdbsum/1nma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nma ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/NRAM_I84A1 NRAM_I84A1] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.
 +
== 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/nm/1nma_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=1nma ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1NMA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Influenza_virus_a/whale/maine/1/84_isolated_from_pilot_whale_(globicephala_melaena) Influenza virus a/whale/maine/1/84 isolated from pilot whale (globicephala melaena)] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NMA OCA].
+
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
-
 
+
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
-
==Reference==
+
__TOC__
-
N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data., Tulip WR, Harley VR, Webster RG, Novotny J, Biochemistry. 1994 Jul 5;33(26):7986-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7517697 7517697]
+
</StructureSection>
-
[[Category: Exo-alpha-sialidase]]
+
[[Category: Influenza A virus]]
-
[[Category: Influenza virus a/whale/maine/1/84 isolated from pilot whale (globicephala melaena)]]
+
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
-
[[Category: Protein complex]]
+
[[Category: Colman PM]]
-
[[Category: Colman, P.M.]]
+
[[Category: Tulip WR]]
-
[[Category: Tulip, W.R.]]
+
[[Category: Varghese JN]]
-
[[Category: Varghese, J.N.]]
+
-
[[Category: NAG]]
+
-
[[Category: complex (hydrolase/immunoglobulin)]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:38:45 2007''
+

Current revision

N9 NEURAMINIDASE COMPLEXES WITH ANTIBODIES NC41 AND NC10: EMPIRICAL FREE-ENERGY CALCULATIONS CAPTURE SPECIFICITY TRENDS OBSERVED WITH MUTANT BINDING DATA

PDB ID 1nma

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1nma"
Personal tools