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| | <StructureSection load='1tjw' size='340' side='right'caption='[[1tjw]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1tjw' size='340' side='right'caption='[[1tjw]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1tjw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Anapl Anapl]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TJW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1tjw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Anas_platyrhynchos Anas platyrhynchos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TJW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS1:ARGININOSUCCINATE'>AS1</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hy1|1hy1]], [[1k7w|1k7w]], [[1dcn|1dcn]], [[1auw|1auw]], [[1hy0|1hy0]], [[1k62|1k62]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS1:ARGININOSUCCINATE'>AS1</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Argininosuccinate_lyase Argininosuccinate lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.1 4.3.2.1] </span></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=1tjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tjw OCA], [https://pdbe.org/1tjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tjw RCSB], [https://www.ebi.ac.uk/pdbsum/1tjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tjw ProSAT]</span></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=1tjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tjw OCA], [https://pdbe.org/1tjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tjw RCSB], [https://www.ebi.ac.uk/pdbsum/1tjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tjw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ARLY2_ANAPL ARLY2_ANAPL]] Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein also functions as an enzymatically active argininosuccinate lyase.<ref>PMID:10029536</ref> <ref>PMID:11698398</ref> <ref>PMID:15320872</ref> <ref>PMID:9369472</ref>
| + | [https://www.uniprot.org/uniprot/ARLY2_ANAPL ARLY2_ANAPL] Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein also functions as an enzymatically active argininosuccinate lyase.<ref>PMID:10029536</ref> <ref>PMID:11698398</ref> <ref>PMID:15320872</ref> <ref>PMID:9369472</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Anapl]] | + | [[Category: Anas platyrhynchos]] |
| - | [[Category: Argininosuccinate lyase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Codding, P W]] | + | [[Category: Codding PW]] |
| - | [[Category: Horvatin, C]] | + | [[Category: Horvatin C]] |
| - | [[Category: Howell, P L]] | + | [[Category: Howell PL]] |
| - | [[Category: Lobsanov, Y D]] | + | [[Category: Lobsanov YD]] |
| - | [[Category: Sampaleanu, L M]] | + | [[Category: Sampaleanu LM]] |
| - | [[Category: Smith, G D]] | + | [[Category: Smith GD]] |
| - | [[Category: Tsai, M]] | + | [[Category: Tsai M]] |
| - | [[Category: Delta 2 crystallin]]
| + | |
| - | [[Category: Enzyme mechanism]]
| + | |
| - | [[Category: Eye lens protein]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
ARLY2_ANAPL Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein also functions as an enzymatically active argininosuccinate lyase.[1] [2] [3] [4]
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
Delta crystallin, a taxon-specific crystallin present in avian eye lenses, is homologous to the urea cycle enzyme ASL (argininosuccinate lyase). Although there are two delta crystallin isoforms in duck lenses, ddeltac1 (duck delta1 crystallin) and ddeltac2 (duck delta2 crystallin), only ddeltac2 is catalytically active. Previous structural studies have suggested that residues Ser283 and His162 in the multi-subunit active site of ddeltac2/ASL are the putative catalytic acid/base, while the highly conserved, positively charged Lys289 is thought to help stabilize the carbanion intermediate. The strict conservation of a small hydroxy-containing residue (Thr or Ser) at position 161 adjacent to the putative catalytic base, as well as its proximity to the substrate in the S283A ddeltac2 enzyme-substrate complex, prompted us to investigate further the role this residue. Structures of the active T161S and inactive T161D ddeltac2 mutants, as well as T161D complexed with argininosuccinate, have been determined to 2.0 A resolution. The structures suggest that a hydroxy group is required at position 161 to help correctly position the side chain of Lys289 and the fumarate moiety of the substrate. Threonine is probably favoured over serine, because the interaction of its methyl group with Leu206 would restrict its conformational flexibility. Residues larger than Thr or Ser interfere with substrate binding, supporting previous suggestions that correct positioning of the substrate's fumarate moiety is essential for catalysis to occur. The presence of the 280s loop (i.e. a loop formed by residues 270-290) in the 'open' conformation suggests that loop closure, thought to be essential for sequestration of the substrate, may be triggered by the formation of the carbanion or aci-carboxylate intermediates, whose charge distribution more closely mimics that of the sulphate ion found in the active-site region of the inactive ddeltac1. The 280s loop in ddeltac1 is in the closed conformation.
Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis.,Sampaleanu LM, Codding PW, Lobsanov YD, Tsai M, Smith GD, Horvatin C, Howell PL Biochem J. 2004 Dec 1;384(Pt 2):437-47. PMID:15320872[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vallee F, Turner MA, Lindley PL, Howell PL. Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate. Biochemistry. 1999 Feb 23;38(8):2425-34. PMID:10029536 doi:10.1021/bi982149h
- ↑ Sampaleanu LM, Yu B, Howell PL. Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase. J Biol Chem. 2002 Feb 8;277(6):4166-75. Epub 2001 Nov 6. PMID:11698398 doi:10.1074/jbc.M107465200
- ↑ Sampaleanu LM, Codding PW, Lobsanov YD, Tsai M, Smith GD, Horvatin C, Howell PL. Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis. Biochem J. 2004 Dec 1;384(Pt 2):437-47. PMID:15320872 doi:10.1042/BJ20040656
- ↑ Abu-Abed M, Turner MA, Vallee F, Simpson A, Slingsby C, Howell PL. Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91. Biochemistry. 1997 Nov 18;36(46):14012-22. PMID:9369472 doi:10.1021/bi971407s
- ↑ Sampaleanu LM, Codding PW, Lobsanov YD, Tsai M, Smith GD, Horvatin C, Howell PL. Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis. Biochem J. 2004 Dec 1;384(Pt 2):437-47. PMID:15320872 doi:10.1042/BJ20040656
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