2hpa: Difference between revisions
New page: left|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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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 NAG, NDG and PT3 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
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