From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1bd4.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1bd4.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1bd4| PDB=1bd4 | SCENE= }} | | {{STRUCTURE_1bd4| PDB=1bd4 | SCENE= }} |
| | | | |
| - | '''UPRT-URACIL COMPLEX'''
| + | ===UPRT-URACIL COMPLEX=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9628859}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9628859 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_9628859}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 34: |
Line 38: |
| | [[Category: Uprt]] | | [[Category: Uprt]] |
| | [[Category: Uracil]] | | [[Category: Uracil]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:21:33 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:52:13 2008'' |
Revision as of 15:52, 30 June 2008
Template:STRUCTURE 1bd4
UPRT-URACIL COMPLEX
Template:ABSTRACT PUBMED 9628859
About this Structure
1BD4 is a Single protein structure of sequence from Toxoplasma gondii. Full crystallographic information is available from OCA.
Reference
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding., Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG, EMBO J. 1998 Jun 15;17(12):3219-32. PMID:9628859
Page seeded by OCA on Mon Jun 30 18:52:13 2008
