| Structural highlights
1l8o 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.
| | Ligands: | ,
| | Related: | 1l8l |
| Activity: | Phosphoserine phosphatase, with EC number 3.1.3.3 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
|
