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| | ==Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase== | | ==Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase== |
| - | <StructureSection load='1l8l' size='340' side='right' caption='[[1l8l]], [[Resolution|resolution]] 2.51Å' scene=''> | + | <StructureSection load='1l8l' size='340' side='right'caption='[[1l8l]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1l8l]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1l8l]] 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=1L8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APO:D-2-AMINO-3-PHOSPHONO-PROPIONIC+ACID'>APO</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]] 2.51Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1l8o|1l8o]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APO:D-2-AMINO-3-PHOSPHONO-PROPIONIC+ACID'>APO</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoserine_phosphatase Phosphoserine phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.3 3.1.3.3] </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=1l8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8l OCA], [https://pdbe.org/1l8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8l RCSB], [https://www.ebi.ac.uk/pdbsum/1l8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8l ProSAT]</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=1l8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8l OCA], [http://pdbe.org/1l8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l8l RCSB], [http://www.ebi.ac.uk/pdbsum/1l8l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SERB_HUMAN SERB_HUMAN]] Defects in PSPH are the cause of phosphoserine phosphatase deficiency (PSPHD)[MIM:[http://omim.org/entry/614023 614023]]. A disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome.<ref>PMID:14673469</ref> | + | [https://www.uniprot.org/uniprot/SERB_HUMAN SERB_HUMAN] Defects in PSPH are the cause of phosphoserine phosphatase deficiency (PSPHD)[MIM:[https://omim.org/entry/614023 614023]. A disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome.<ref>PMID:14673469</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SERB_HUMAN SERB_HUMAN]] Catalyzes the last step in the biosynthesis of serine from carbohydrates. The reaction mechanism proceeds via the formation of a phosphoryl-enzyme intermediates.<ref>PMID:12777757</ref> | + | [https://www.uniprot.org/uniprot/SERB_HUMAN SERB_HUMAN] Catalyzes the last step in the biosynthesis of serine from carbohydrates. The reaction mechanism proceeds via the formation of a phosphoryl-enzyme intermediates.<ref>PMID:12777757</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1l8l" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1l8l" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphoserine phosphatase|Phosphoserine phosphatase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoserine phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Heo, Y S]] | + | [[Category: Heo YS]] |
| - | [[Category: Hwang, K Y]] | + | [[Category: Hwang KY]] |
| - | [[Category: Jeon, Y H]] | + | [[Category: Jeon YH]] |
| - | [[Category: Kim, H Y]] | + | [[Category: Kim HY]] |
| - | [[Category: Kim, J H]] | + | [[Category: Kim JH]] |
| - | [[Category: Lee, T G]] | + | [[Category: Lee TG]] |
| - | [[Category: Moon, J]] | + | [[Category: Moon J]] |
| - | [[Category: Park, M H]] | + | [[Category: Park MH]] |
| - | [[Category: Park, S Y]] | + | [[Category: Park SY]] |
| - | [[Category: Ro, S]] | + | [[Category: Ro S]] |
| - | [[Category: Conformational rearrangement]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| Structural highlights
Disease
SERB_HUMAN Defects in PSPH are the cause of phosphoserine phosphatase deficiency (PSPHD)[MIM:614023. A disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome.[1]
Function
SERB_HUMAN Catalyzes the last step in the biosynthesis of serine from carbohydrates. The reaction mechanism proceeds via the formation of a phosphoryl-enzyme intermediates.[2]
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
Human phosphoserine phosphatase (HPSP) regulates the levels of glycine and d-serine, the putative co-agonists for the glycine site of the NMDA receptor in the brain. Here, we describe the first crystal structures of the HPSP in complexes with the competitive inhibitor 2-amino-3-phosphonopropionic acid (AP3) at 2.5 A, and the phosphate ion (Pi) and the product uncompetitive inhibitor l-serine (HPSP.l-Ser.Pi) at 2.8 A. The complex structures reveal that the open-closed environmental change of the active site, generated by local rearrangement of the alpha-helical bundle domain, is important to substrate recognition and hydrolysis. The maximal extent of this structural rearrangement is shown to be about 13 A at the L4 loop and about 25 degrees at the helix alpha3. Both the structural change and mutagenesis data suggest that Arg-65 and Glu-29 play an important role in the binding of the substrate. Interestingly, the AP3 binding mode turns out to be significantly different from that of the natural substrate, phospho-l-serine, and the HPSP.l-Ser.Pi structure provides a structural basis for the feedback control mechanism of serine. These analyses allow us to provide a clear model for the mechanism of HPSP and a framework for structure-based drug development.
Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase.,Kim HY, Heo YS, Kim JH, Park MH, Moon J, Kim E, Kwon D, Yoon J, Shin D, Jeong EJ, Park SY, Lee TG, Jeon YH, Ro S, Cho JM, Hwang KY J Biol Chem. 2002 Nov 29;277(48):46651-8. Epub 2002 Sep 3. PMID:12213811[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Veiga-da-Cunha M, Collet JF, Prieur B, Jaeken J, Peeraer Y, Rabbijns A, Van Schaftingen E. Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet. 2004 Feb;12(2):163-6. PMID:14673469 doi:10.1038/sj.ejhg.5201083
- ↑ Peeraer Y, Rabijns A, Verboven C, Collet JF, Van Schaftingen E, De Ranter C. High-resolution structure of human phosphoserine phosphatase in open conformation. Acta Crystallogr D Biol Crystallogr. 2003 Jun;59(Pt 6):971-7. Epub 2003, May 23. PMID:12777757
- ↑ Kim HY, Heo YS, Kim JH, Park MH, Moon J, Kim E, Kwon D, Yoon J, Shin D, Jeong EJ, Park SY, Lee TG, Jeon YH, Ro S, Cho JM, Hwang KY. Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase. J Biol Chem. 2002 Nov 29;277(48):46651-8. Epub 2002 Sep 3. PMID:12213811 doi:10.1074/jbc.M204866200
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