2glq

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[[Image:2glq.gif|left|200px]]<br /><applet load="2glq" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2glq.gif|left|200px]]
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caption="2glq, resolution 1.60&Aring;" />
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'''X-ray structure of human alkaline phosphatase in complex with strontium'''<br />
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{{Structure
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|PDB= 2glq |SIZE=350|CAPTION= <scene name='initialview01'>2glq</scene>, resolution 1.60&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=SR:STRONTIUM ION'>SR</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1]
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|GENE=
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}}
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'''X-ray structure of human alkaline phosphatase in complex with strontium'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2GLQ 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=NAG:'>NAG</scene>, <scene name='pdbligand=PO3:'>PO3</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=SR:'>SR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alkaline_phosphatase Alkaline phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.1 3.1.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GLQ OCA].
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2GLQ 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=2GLQ OCA].
==Reference==
==Reference==
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Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones., Llinas P, Masella M, Stigbrand T, Menez A, Stura EA, Le Du MH, Protein Sci. 2006 Jul;15(7):1691-700. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16815919 16815919]
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Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones., Llinas P, Masella M, Stigbrand T, Menez A, Stura EA, Le Du MH, Protein Sci. 2006 Jul;15(7):1691-700. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16815919 16815919]
[[Category: Alkaline phosphatase]]
[[Category: Alkaline phosphatase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: structure-function]]
[[Category: structure-function]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:55 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:06:09 2008''

Revision as of 15:06, 20 March 2008

Image:2glq.gif


PDB ID 2glq

Drag the structure with the mouse to rotate
, resolution 1.60Å
Ligands: , , , and
Activity: Alkaline phosphatase, with EC number 3.1.3.1
Coordinates: save as pdb, mmCIF, xml



X-ray structure of human alkaline phosphatase in complex with strontium


Contents

Overview

Strontium is used in the treatment of osteoporosis as a ranelate compound, and in the treatment of painful scattered bone metastases as isotope. At very high doses and in certain conditions, it can lead to osteomalacia characterized by impairment of bone mineralization. The osteomalacia symptoms resemble those of hypophosphatasia, a rare inherited disorder associated with mutations in the gene encoding for tissue-nonspecific alkaline phosphatase (TNAP). Human alkaline phosphatases have four metal binding sites--two for zinc, one for magnesium, and one for calcium ion--that can be substituted by strontium. Here we present the crystal structure of strontium-substituted human placental alkaline phosphatase (PLAP), a related isozyme of TNAP, in which such replacement can have important physiological implications. The structure shows that strontium substitutes the calcium ion with concomitant modification of the metal coordination. The use of the flexible and polarizable force-field TCPEp (topological and classical polarization effects for proteins) predicts that calcium or strontium has similar interaction energies at the calcium-binding site of PLAP. Since calcium helps stabilize a large area that includes loops 210-228 and 250-297, its substitution by strontium could affect the stability of this region. Energy calculations suggest that only at high doses of strontium, comparable to those found for calcium, can strontium substitute for calcium. Since osteomalacia is observed after ingestion of high doses of strontium, alkaline phosphatase is likely to be one of the targets of strontium, and thus this enzyme might be involved in this disease.

Disease

Known disease associated with this structure: Osteoarthritis, susceptibility to OMIM:[608135]

About this Structure

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

Reference

Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones., Llinas P, Masella M, Stigbrand T, Menez A, Stura EA, Le Du MH, Protein Sci. 2006 Jul;15(7):1691-700. PMID:16815919

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