2hwb

From Proteopedia

(Difference between revisions)

Revision as of 07:55, 4 July 2018

A comparison of the anti-rhinoviral drug binding pocket in hrv14 and hrv1a

Structural highlights

2hwb is a 4 chain structure with sequence from Hrv-14. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLG_HRV14] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (By similarity). The capsid interacts with human ICAM1 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis. VP0 precursor is a component of immature procapsids (By similarity). Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription (By similarity). Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).

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

The three-dimensional structures of two human rhinovirus serotypes (HRV14 and HRV1A) are compared when complexed with various antiviral agents. Although these agents all bind into the same hydrophobic pocket, the exact viral-drug interactions differ. In the absence of drugs, the pocket is occupied by a fatty acid in HRV1A, but is empty in HRV14 except for two water molecules. The conformation of each drug is dependent upon the shape of the hydrophobic pocket. In HRV14 the major residues determining the shape of the binding site are Y1128, P1174 and M1224, corresponding to I1125, M1169 and I1220 in HRV1A. When there is no cofactor or a drug in the pocket, the entrance to the pocket is open. However, the entrance is closed when the pocket is occupied by a cofactor or a drug. There are relatively small conformational changes when the agents displace the natural cofactor in HRV1A. In contrast, there are much larger conformational changes on binding a drug in HRV14. These differences cause an inhibition of viral attachment in HRV14 but not in HRV1A. Binding of the drugs results in three additional interprotomer hydrogen bonds in HRV14 and one in HRV1A. These hydrogen bonds and a potential loss of flexibility upon efficient packing of the pocket may contribute to the inhibition of uncoating in both serotypes.

A comparison of the anti-rhinoviral drug binding pocket in HRV14 and HRV1A.,Kim KH, Willingmann P, Gong ZX, Kremer MJ, Chapman MS, Minor I, Oliveira MA, Rossmann MG, Andries K, Diana GD, et al. J Mol Biol. 1993 Mar 5;230(1):206-27. PMID:8383771^[1]

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

References

↑ Kim KH, Willingmann P, Gong ZX, Kremer MJ, Chapman MS, Minor I, Oliveira MA, Rossmann MG, Andries K, Diana GD, et al.. A comparison of the anti-rhinoviral drug binding pocket in HRV14 and HRV1A. J Mol Biol. 1993 Mar 5;230(1):206-27. PMID:8383771

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/2hwb"

@@ Line 1: / Line 1: @@
-==A COMPARISON OF THE ANTI-RHINOVIRAL DRUG BINDING POCKET IN HRV14 AND HRV1A==
+==A comparison of the anti-rhinoviral drug binding pocket in hrv14 and hrv1a==
 <StructureSection load='2hwb' size='340' side='right' caption='[[2hwb]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2hwb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrv-14 Hrv-14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HWB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HWB FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=W91:5-(3-(2,6-DICHLORO-4-(4,5-DIHYDRO-2-OXAZOLYL)PHENOXY)PROPYL)-3-METHYL+ISOXAZOLE'>W91</scene></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=2hwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwb OCA], [http://pdbe.org/2hwb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hwb RCSB], [http://www.ebi.ac.uk/pdbsum/2hwb 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=2hwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hwb OCA], [http://pdbe.org/2hwb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hwb RCSB], [http://www.ebi.ac.uk/pdbsum/2hwb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hwb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/2hwb_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/2hwb_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2hwb ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2hwb

From Proteopedia

Revision as of 07:55, 4 July 2018

A comparison of the anti-rhinoviral drug binding pocket in hrv14 and hrv1a

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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