1f57: Difference between revisions
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New page: left|200px<br /><applet load="1f57" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f57, resolution 1.75Å" /> '''CARBOXYPEPTIDASE A C... |
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[[Image:1f57.jpg|left|200px]]<br /><applet load="1f57" size=" | [[Image:1f57.jpg|left|200px]]<br /><applet load="1f57" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1f57, resolution 1.75Å" /> | caption="1f57, resolution 1.75Å" /> | ||
'''CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A'''<br /> | '''CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A'''<br /> | ||
==Overview== | ==Overview== | ||
D-Cysteine differs from the antiarthritis drug D-penicillamine by only two | D-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct mechanism: D-cysteine binds tightly to the active site zinc, while D-penicillamine catalyzes metal removal. To investigate the structural basis for this difference, we solved the crystal structure of carboxypeptidase A complexed with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. The structure explains the difference in potency between D-Cys and L-Cys and provides insight into the mechanism of D-penicillamine inhibition. D-Cys binding induces a concerted motion of the side chains around the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal structures and along a limited path. Analysis of concerted motions of CPD and CPD-inhibitor crystal structures reveals a clustering of these structures into distinct groups. Using the restricted conformational flexibility of a drug target in this type of analysis could greatly enhance efficiency in drug design. | ||
==About this Structure== | ==About this Structure== | ||
1F57 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and DCY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http:// | 1F57 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=DCY:'>DCY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F57 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Carboxypeptidase A]] | [[Category: Carboxypeptidase A]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Aalten, D | [[Category: Aalten, D M.van.]] | ||
[[Category: Chong, C | [[Category: Chong, C R.]] | ||
[[Category: Joshua-Tor, L.]] | [[Category: Joshua-Tor, L.]] | ||
[[Category: DCY]] | [[Category: DCY]] | ||
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[[Category: metalloprotease inhibitor]] | [[Category: metalloprotease inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:34:59 2008'' | ||
