2hpa
From Proteopedia
(New page: 200px<br /> <applet load="2hpa" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hpa, resolution 2.90Å" /> '''STRUCTURAL ORIGINS ...) |
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| - | [[Image:2hpa.gif|left|200px]]<br /> | + | [[Image:2hpa.gif|left|200px]]<br /><applet load="2hpa" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2hpa, resolution 2.90Å" /> | caption="2hpa, resolution 2.90Å" /> | ||
'''STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE'''<br /> | '''STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Acid phosphatase activity in the blood serum is usually separated into | + | Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 A resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. (1993) J. Biol. Chem. 268, 20744-20746) erroneously positioned D-tartrate into the active site. Modeling studies have shown that the C3 hydroxyl group on the D(-)-stereoisomer of tartrate, which does not significantly inhibit prostatic acid phosphatase, does not form strong hydrogen bonds with Arg-79 or His-257. The structure of human prostatic acid phosphatase, noncovalently bound in N-propyl-L-tartramate, is used to develop inhibitors with higher specificity and potency than L(+)-tartrate. |
==About this Structure== | ==About this Structure== | ||
| - | 2HPA 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 NAG, NDG and PT3 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acid_phosphatase Acid phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.2 3.1.3.2] Full crystallographic information is available from [http:// | + | 2HPA 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=NDG:'>NDG</scene> and <scene name='pdbligand=PT3:'>PT3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acid_phosphatase Acid phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.2 3.1.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HPA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Handy, G.]] | [[Category: Handy, G.]] | ||
| - | [[Category: Lacount, M | + | [[Category: Lacount, M W.]] |
[[Category: Lebioda, L.]] | [[Category: Lebioda, L.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: n-propyltartramate]] | [[Category: n-propyltartramate]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:44:16 2008'' |
Revision as of 15:44, 21 February 2008
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STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE
Overview
Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 A resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. (1993) J. Biol. Chem. 268, 20744-20746) erroneously positioned D-tartrate into the active site. Modeling studies have shown that the C3 hydroxyl group on the D(-)-stereoisomer of tartrate, which does not significantly inhibit prostatic acid phosphatase, does not form strong hydrogen bonds with Arg-79 or His-257. The structure of human prostatic acid phosphatase, noncovalently bound in N-propyl-L-tartramate, is used to develop inhibitors with higher specificity and potency than L(+)-tartrate.
About this Structure
2HPA is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Acid phosphatase, with EC number 3.1.3.2 Full crystallographic information is available from OCA.
Reference
Structural origins of L(+)-tartrate inhibition of human prostatic acid phosphatase., LaCount MW, Handy G, Lebioda L, J Biol Chem. 1998 Nov 13;273(46):30406-9. PMID:9804805
Page seeded by OCA on Thu Feb 21 17:44:16 2008
Categories: Acid phosphatase | Homo sapiens | Single protein | Handy, G. | Lacount, M W. | Lebioda, L. | NAG | NDG | PT3 | N-propyltartramate
