1l5r: Difference between revisions

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==Human liver glycogen phosphorylase a complexed with riboflavin, N-Acetyl-beta-D-Glucopyranosylamine and CP-403,700==
The line below this paragraph, containing "STRUCTURE_1l5r", creates the "Structure Box" on the page.
<StructureSection load='1l5r' size='340' side='right'caption='[[1l5r]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1l5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L5R FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=RBF:RIBOFLAVIN'>RBF</scene></td></tr>
{{STRUCTURE_1l5r| PDB=1l5r |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l5r OCA], [https://pdbe.org/1l5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l5r RCSB], [https://www.ebi.ac.uk/pdbsum/1l5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l5r ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:[https://omim.org/entry/232700 232700]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.<ref>PMID:9529348</ref>
== Function ==
[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
== 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/l5/1l5r_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=1l5r ConSurf].
<div style="clear:both"></div>


'''Human liver glycogen phosphorylase a complexed with riboflavin, N-Acetyl-beta-D-Glucopyranosylamine and CP-403,700'''
==See Also==
 
*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
 
== References ==
==Overview==
<references/>
Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of glycogen to maintain serum glucose levels and is a therapeutic target for diabetes. HLGP is regulated by multiple interacting allosteric sites, each of which is a potential drug binding site. We used surface plasmon resonance (SPR) to screen for compounds that bind to the purine allosteric inhibitor site. We determined the affinities of a series of compounds and solved the crystal structures of three representative ligands with K(D) values from 17-550 microM. The crystal structures reveal that the affinities are partly determined by ligand-specific water-mediated hydrogen bonds and side chain movements. These effects could not be predicted; both crystallographic and SPR studies were required to understand the important features of binding and together provide a basis for the design of new allosteric inhibitors targeting this site.
__TOC__
 
</StructureSection>
==About this Structure==
1L5R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L5R OCA].
 
==Reference==
Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase., Ekstrom JL, Pauly TA, Carty MD, Soeller WC, Culp J, Danley DE, Hoover DJ, Treadway JL, Gibbs EM, Fletterick RJ, Day YS, Myszka DG, Rath VL, Chem Biol. 2002 Aug;9(8):915-24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12204691 12204691]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Carty MD]]
[[Category: Carty, M D.]]
[[Category: Culp J]]
[[Category: Culp, J.]]
[[Category: Danley DE]]
[[Category: Danley, D E.]]
[[Category: Day YSN]]
[[Category: Day, Y S.N.]]
[[Category: Ekstrom JL]]
[[Category: Ekstrom, J L.]]
[[Category: Fletterick RJ]]
[[Category: Fletterick, R J.]]
[[Category: Gibbs EM]]
[[Category: Gibbs, E M.]]
[[Category: Hoover DJ]]
[[Category: Hoover, D J.]]
[[Category: Myszka DG]]
[[Category: Myszka, D G.]]
[[Category: Pauly TA]]
[[Category: Pauly, T A.]]
[[Category: Rath VL]]
[[Category: Rath, V L.]]
[[Category: Soeller WC]]
[[Category: Soeller, W C.]]
[[Category: Treadway JL]]
[[Category: Treadway, J L.]]
[[Category: Phosphorylase]]
[[Category: Purine site]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 23:34:14 2008''

Latest revision as of 11:06, 3 April 2024

Human liver glycogen phosphorylase a complexed with riboflavin, N-Acetyl-beta-D-Glucopyranosylamine and CP-403,700Human liver glycogen phosphorylase a complexed with riboflavin, N-Acetyl-beta-D-Glucopyranosylamine and CP-403,700

Structural highlights

1l5r is a 2 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 2.1Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PYGL_HUMAN Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.[1]

Function

PYGL_HUMAN Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.

Evolutionary Conservation

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

See Also

References

  1. Burwinkel B, Bakker HD, Herschkovitz E, Moses SW, Shin YS, Kilimann MW. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. 1998 Apr;62(4):785-91. PMID:9529348

1l5r, resolution 2.10Å

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