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1y2m

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Revision as of 07:27, 18 April 2018

Crystal structure of phenylalanine ammonia-lyase from yeast Rhododporidium toruloides

Structural highlights

1y2m is a 4 chain structure with sequence from Cbs 6016. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Activity:	Lyase, with EC number 4.3.1.24 and 4.3.1.25 4.3.1.23, 4.3.1.24 and 4.3.1.25
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PALY_RHOTO] Catalyzes the non-oxidative deamination of L-phenylalanine and L-tyrosine to form trans-cinnamic acid and p-coumaric acid respectively with similar efficiencies. Facilitates the commitment step in phenylpropanoid pathways that produce lignins, coumarins and flavonoids.^[1]

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

Structure-based protein engineering coupled with chemical modifications (e.g., pegylation) is a powerful combination to significantly improve the development of proteins as therapeutic agents. As a test case, phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) was selected for enzyme replacement therapy in phenylketonuria [C.R. Scriver, S. Kaufman, Hyperphenylalaninemia:phenylalanine Hydroxylase Deficiency. The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, Chapter 77], an inherited metabolic disorder (OMIM 261600) causing mental retardation due to deficiency of the enzyme l-phenylalanine hydroxylase (EC 1.14.16.1). Previous in vivo studies of recombinant PAL demonstrated a lowering of blood l-phenylalanine levels; yet, the metabolic effect was not sustained due to protein degradation and immunogenicity [C.N. Sarkissian, Z. Shao, F. Blain, R. Peevers, H. Su, R. Heft, T.M. Chang, C.R. Scriver, A different approach to treatment of phenylketonuria:phenylalanine degradation with recombinant phenylalanine ammonia lyase, Proc. Natl. Acad. Sci. USA 96 (1999) 2339; J.A. Hoskins, G. Jack, H.E. Wade, R.J. Peiris, E.C. Wright, D.J. Starr, J. Stern, Enzymatic control of phenylalanine intake in phenylketonuria, Lancet 1 (1980) 392; C.M. Ambrus, S. Anthone, C. Horvath, K. Kalghatgi, A.S. Lele, G. Eapen, J.L. Ambrus, A.J. Ryan, P. Li, Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria, Ann. Intern. Med. 106 (1987) 531]. Here, we report the 1.6A three-dimensional structure of Rhodosporidium toruloides PAL, structure-based molecular engineering, pegylation of PAL, as well as in vitro and in vivo PKU mouse model studies on pegylated PAL formulations. Our results show that pegylation of R. toruloides PAL leads to promising therapeutic efficacy after subcutaneous injection by enhancing the in vivo activity, lowering plasma phenylalanine, and leading to reduced immunogenicity. The three-dimensional structure of PAL provides a basis for understanding the properties of pegylated forms of PAL and strategies for structure-based re-engineering of PAL for PKU treatment.

Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria.,Wang L, Gamez A, Sarkissian CN, Straub M, Patch MG, Han GW, Striepeke S, Fitzpatrick P, Scriver CR, Stevens RC Mol Genet Metab. 2005 Sep-Oct;86(1-2):134-40. Epub 2005 Jul 11. PMID:16006165^[2]

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

References

↑ Hodgins DS. Yeast phenylalanine ammonia-lyase. Purification, properties, and the identification of catalytically essential dehydroalanine. J Biol Chem. 1971 May 10;246(9):2977-85. PMID:5102931
↑ Wang L, Gamez A, Sarkissian CN, Straub M, Patch MG, Han GW, Striepeke S, Fitzpatrick P, Scriver CR, Stevens RC. Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria. Mol Genet Metab. 2005 Sep-Oct;86(1-2):134-40. Epub 2005 Jul 11. PMID:16006165 doi:10.1016/j.ymgme.2005.05.012

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/1y2m"

@@ Line 1: / Line 1: @@
 ==Crystal structure of phenylalanine ammonia-lyase from yeast Rhododporidium toruloides==
 <StructureSection load='1y2m' size='340' side='right' caption='[[1y2m]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lyase Lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.1.23, 4.3.1.24 and 4.3.1.25 4.3.1.23, 4.3.1.24 and 4.3.1.25] </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=1y2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2m OCA], [http://pdbe.org/1y2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y2m RCSB], [http://www.ebi.ac.uk/pdbsum/1y2m 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=1y2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2m OCA], [http://pdbe.org/1y2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y2m RCSB], [http://www.ebi.ac.uk/pdbsum/1y2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y2m ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y2/1y2m_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y2/1y2m_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1y2m

From Proteopedia

Revision as of 07:27, 18 April 2018

Crystal structure of phenylalanine ammonia-lyase from yeast Rhododporidium toruloides

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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