1l8l

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{{STRUCTURE_1l8l| PDB=1l8l | SCENE= }}
{{STRUCTURE_1l8l| PDB=1l8l | SCENE= }}
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'''Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase'''
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===Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_12213811}}
==About this Structure==
==About this Structure==
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[[Category: Conformational rearrangement]]
[[Category: Conformational rearrangement]]
[[Category: Phosphatase]]
[[Category: Phosphatase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:40:07 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:57:23 2008''

Revision as of 08:57, 2 July 2008

Image:1l8l.png

Template:STRUCTURE 1l8l

Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase

Template:ABSTRACT PUBMED 12213811

About this Structure

1L8L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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