6l6e

From Proteopedia

Human PDE5 catalytic core in complex with avanafil

Structural highlights

6l6e is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.92Å
Ligands:	E6L, MG, SO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.

Publication Abstract from PubMed

Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein-drug interactions revealed the structural basis of avanafil's superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent alpha-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting alpha-helix backbone in structure-based drug design.

Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting alpha-Helix Backbone Oxygen by Halogen Bonding.,Hsieh CM, Chen CY, Chern JW, Chan NL J Med Chem. 2020 Aug 13;63(15):8485-8494. doi: 10.1021/acs.jmedchem.0c00853. Epub, 2020 Jul 27. PMID:32663396^[1]

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

Loading citation details..

Citations

1 reviews cite this structure

Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases.

Cote et al. (2022)

0 more

1 other articles

No citations found

References

↑ Hsieh CM, Chen CY, Chern JW, Chan NL. Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding. J Med Chem. 2020 Aug 13;63(15):8485-8494. PMID:32663396 doi:10.1021/acs.jmedchem.0c00853

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

loadScript /wiki/extensions/jsmol/j2s/core/package.js

loadScript /wiki/extensions/jsmol/j2s/core/corejmol.z.js

loadScript /wiki/extensions/jsmol/j2s/J/translation/PO.js

loadScript /wiki/extensions/jsmol/j2s/core/corescript.z.js

JSmol exec jmolApplet1 start applet null

Jmol JavaScript applet jmolApplet1__13086286955827475__ initializing

Jmol getValue debug null

Jmol getValue logLevel null

Jmol getValue allowjavascript null

AppletRegistry.checkIn(jmolApplet1__13086286955827475__)

vwrOptions:

{ "name":"jmolApplet1","applet":true,"documentBase":"https://proteopedia.org/wiki/index.php/6l6e","platform":"J.awtjs2d.Platform","fullName":"jmolApplet1__13086286955827475__","codePath":"https:/wiki/extensions/jsmol/j2s/","display":"jmolApplet1_canvas2d","loadStructCallback":"manageLoadStructCallback","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol object]","syncId":"13086286955827475","messageCallback":"msgCb","bgcolor":"white" }

setting document base to "https://proteopedia.org/wiki/index.php/6l6e"

Jmol Version: 14.31.8 2020-09-26 10:04

java.vendor: Java2Script (HTML5)

java.version: 2019-06-08 00:17:46 (JSmol/j2s)

os.name: Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)

Access: ALL

memory: 0.0/0.0

processors available: 1

useCommandThread: false

appletId:jmolApplet1 (signed)

Jmol getValue emulate null

defaults = "Jmol"

Jmol getValue boxbgcolor null

Jmol getValue bgcolor white

backgroundColor = "white"

Jmol getValue ANIMFRAMECallback null

Jmol getValue APPLETREADYCallback Jmol._readyCallback

APPLETREADYCallback = "Jmol._readyCallback"

StatusManager callback set for APPLETREADYCallback f=Jmol._readyCallback cb=APPLETREADY

Jmol getValue ATOMMOVEDCallback null

Jmol getValue AUDIOCallback null

Jmol getValue CLICKCallback null

Jmol getValue DRAGDROPCallback null

Jmol getValue ECHOCallback null

Jmol getValue ERRORCallback null

Jmol getValue EVALCallback null

Jmol getValue HOVERCallback null

Jmol getValue IMAGECallback null

Jmol getValue LOADSTRUCTCallback manageLoadStructCallback

LOADSTRUCTCallback = "manageLoadStructCallback"

StatusManager callback set for LOADSTRUCTCallback f=manageLoadStructCallback cb=LOADSTRUCT

Jmol getValue MEASURECallback null

Jmol getValue MESSAGECallback msgCb

MESSAGECallback = "msgCb"

StatusManager callback set for MESSAGECallback f=msgCb cb=MESSAGE

Jmol getValue MINIMIZATIONCallback null

Jmol getValue SERVICECallback null

Jmol getValue PICKCallback null

Jmol getValue RESIZECallback null

Jmol getValue SCRIPTCallback null

Jmol getValue SYNCCallback null

Jmol getValue STRUCTUREMODIFIEDCallback null

Jmol getValue doTranslate null

language=en_US

Jmol getValue doTranslate null

Note -- Presence of message callback disables disable translation; to enable message translation use jmolSetTranslation(true) prior to jmolApplet()

Note -- language translation disabled

Jmol getValue popupMenu null

Jmol getValue script null

Jmol getValue loadInline null

Jmol getValue load null

Jmol applet jmolApplet1__13086286955827475__ ready

script 1 started

pdbGetHeader = true

FileManager opening url https://proteopedia.org/wiki/extensions/Proteopedia/spt/functions.spt?1733933141

loadScript /wiki/extensions/jsmol/j2s/core/coretext.z.js

Loading, please wait ...

platformSpeed = 8

loadScript /wiki/extensions/jsmol/j2s/core/corescriptmath.z.js

loadScript /wiki/extensions/jsmol/j2s/J/bspt/PointIterator.js

FileManager opening url https://proteopedia.org/cgi-bin/infopdb?6l6e

loadScript /wiki/extensions/jsmol/j2s/JU/JSJSONParser.js

loadScript /wiki/extensions/jsmol/j2s/JU/JSONException.js

JSON parser cannot parse NetworkError

Data for 6l6e could not be found.- Using defaults.

cache cleared

[Step 1] pdb_features.ca_p_only is: integer 0

Loading, please wait ...

PDB ID 6l6e

Drag the structure with the mouse to rotate

Export Animated Image

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6l6e"

Categories: Homo sapiens | Large Structures | Chan NL | Hsieh CM

6l6e

From Proteopedia

Human PDE5 catalytic core in complex with avanafil

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox