1l8l
From Proteopedia
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Molecular basis for the local confomational rearrangement of human phosphoserine phosphatase
Overview
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.
About this Structure
1L8L is a Single protein structure of sequence from Homo sapiens with APO as ligand. Active as Phosphoserine phosphatase, with EC number 3.1.3.3 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
Page seeded by OCA on Mon Nov 12 17:57:45 2007
