2h07

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[[Image:2h07.jpg|left|200px]]<br /><applet load="2h07" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2h07.jpg|left|200px]]
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caption="2h07, resolution 2.20&Aring;" />
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'''crystal structure of human phosphoribosyl pyrophosphate synthetase 1 mutant S132A'''<br />
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{{Structure
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|PDB= 2h07 |SIZE=350|CAPTION= <scene name='initialview01'>2h07</scene>, resolution 2.20&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Ribose-phosphate_diphosphokinase Ribose-phosphate diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.1 2.7.6.1]
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|GENE= PRPS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''crystal structure of human phosphoribosyl pyrophosphate synthetase 1 mutant S132A'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2H07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ribose-phosphate_diphosphokinase Ribose-phosphate diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.1 2.7.6.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H07 OCA].
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2H07 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H07 OCA].
==Reference==
==Reference==
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Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site., Li S, Lu Y, Peng B, Ding J, Biochem J. 2007 Jan 1;401(1):39-47. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16939420 16939420]
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Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site., Li S, Lu Y, Peng B, Ding J, Biochem J. 2007 Jan 1;401(1):39-47. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16939420 16939420]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ribose-phosphate diphosphokinase]]
[[Category: Ribose-phosphate diphosphokinase]]
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[[Category: prs1]]
[[Category: prs1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:36:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:10:57 2008''

Revision as of 15:10, 20 March 2008


PDB ID 2h07

Drag the structure with the mouse to rotate
, resolution 2.20Å
Ligands:
Gene: PRPS1 (Homo sapiens)
Activity: Ribose-phosphate diphosphokinase, with EC number 2.7.6.1
Coordinates: save as pdb, mmCIF, xml



crystal structure of human phosphoribosyl pyrophosphate synthetase 1 mutant S132A


Contents

Overview

PRPP (phosphoribosylpyrophosphate) is an important metabolite essential for nucleotide synthesis and PRS (PRPP synthetase) catalyses synthesis of PRPP from R5P (ribose 5-phosphate) and ATP. The enzymatic activity of PRS is regulated by phosphate ions, divalent metal cations and ADP. In the present study we report the crystal structures of recombinant human PRS1 in complexes with SO4(2-) ions alone and with ATP, Cd2+ and SO4(2-) ions respectively. The AMP moiety of ATP binds at the ATP-binding site, and a Cd2+ ion binds at the active site and in a position to interact with the beta- and gamma-phosphates of ATP. A SO4(2-) ion, an analogue of the activator phosphate, was found to bind at both the R5P-binding site and the allosteric site defined previously. In addi-tion, an extra SO4(2-) binds at a site at the dimer interface between the ATP-binding site and the allosteric site. Binding of this SO4(2-) stabilizes the conformation of the flexible loop at the active site, leading to the formation of the active, open conformation which is essential for binding of ATP and initiation of the catalytic reaction. This is the first time that structural stabilization at the active site caused by binding of an activator has been observed. Structural and biochemical data show that mutations of some residues at this site influence the binding of SO4(2-) and affect the enzymatic activity. The results in the present paper suggest that this new SO4(2-)-binding site is a second allosteric site to regulate the enzymatic activity which might also exist in other eukaryotic PRSs (except plant PRSs of class II), but not in bacterial PRSs.

Disease

Known diseases associated with this structure: Arts syndrome OMIM:[311850], Charcot-Marie-Tooth disease, X-linked recessive, 5 OMIM:[311850], Gout, PRPS-related OMIM:[311850], Phosphoribosylpyrophosphate synthetase superactivity OMIM:[311850]

About this Structure

2H07 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site., Li S, Lu Y, Peng B, Ding J, Biochem J. 2007 Jan 1;401(1):39-47. PMID:16939420

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