1bd3: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="1bd3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bd3, resolution 1.93Å" /> '''STRUCTURE OF THE APO... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1bd3.gif|left|200px]]<br /><applet load="1bd3" size=" | [[Image:1bd3.gif|left|200px]]<br /><applet load="1bd3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1bd3, resolution 1.93Å" /> | caption="1bd3, resolution 1.93Å" /> | ||
'''STRUCTURE OF THE APO URACIL PHOSPHORIBOSYLTRANSFERASE, 2 MUTANT C128V'''<br /> | '''STRUCTURE OF THE APO URACIL PHOSPHORIBOSYLTRANSFERASE, 2 MUTANT C128V'''<br /> | ||
==Overview== | ==Overview== | ||
Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a | Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target for antiparasitic drug design. To aid in structure-based drug design studies against toxoplasmosis, the crystal structures of the T.gondii apo UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil (2.3 A resolution), have been determined. These structures reveal that UPRTase recognizes uracil through polypeptide backbone hydrogen bonds to the uracil exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen hydrogen bond. This stereochemical arrangement and the architecture of the uracil-binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at ring position 5 larger than fluorine, including thymine, cannot bind to the enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at the tip of this arm, functions to cap the active site of its dimer mate, thereby inhibiting the escape of the substrate-binding water molecule. | ||
==About this Structure== | ==About this Structure== | ||
1BD3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] with PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] Full crystallographic information is available from [http:// | 1BD3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] with <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD3 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
[[Category: Uracil phosphoribosyltransferase]] | [[Category: Uracil phosphoribosyltransferase]] | ||
[[Category: Brennan, R | [[Category: Brennan, R G.]] | ||
[[Category: Carter, D.]] | [[Category: Carter, D.]] | ||
[[Category: Roos, D.]] | [[Category: Roos, D.]] | ||
[[Category: Schumacher, M | [[Category: Schumacher, M A.]] | ||
[[Category: Scott, D.]] | [[Category: Scott, D.]] | ||
[[Category: Ullman, B.]] | [[Category: Ullman, B.]] | ||
| Line 25: | Line 25: | ||
[[Category: uprtase]] | [[Category: uprtase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:53:59 2008'' | ||
