1i5e
From Proteopedia
(New page: 200px<br /><applet load="1i5e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i5e, resolution 3.0Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1i5e.gif|left|200px]]<br /><applet load="1i5e" size=" | + | [[Image:1i5e.gif|left|200px]]<br /><applet load="1i5e" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1i5e, resolution 3.0Å" /> | caption="1i5e, resolution 3.0Å" /> | ||
'''CRYSTAL STRUCTURE OF BACILLUS CALDOLYTICUS URACIL PHOSPHORIBOSYLTRANSFERASE WITH BOUND UMP'''<br /> | '''CRYSTAL STRUCTURE OF BACILLUS CALDOLYTICUS URACIL PHOSPHORIBOSYLTRANSFERASE WITH BOUND UMP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Uracil phosphoribosyltransferase (UPRTase) is part of the salvage pathway | + | Uracil phosphoribosyltransferase (UPRTase) is part of the salvage pathway that leads to the biosynthesis of UMP. It catalyzes the formation of UMP and pyrophosphate from uracil and alpha-D-5-phosphoribosyl-1-pyrophosphate. Unlike enzymes in the de novo synthesis of UMP, UPRTases have only been found in lower organisms and are therefore potential targets for the development of new antibiotics. UPRTase from Bacillus caldolyticus has been crystallized and the structure has been determined by isomorphous replacement and refined to 3.0 A resolution. UPRTase from B. caldolyticus forms a dimer with the active sites pointing away from each other. A long arm from each subunit wraps around the other subunit, contributing half of the dimer interface. The monomer adopts the phosphoribosyltransferase type I fold, with a small C-terminal hood defining the uracil-binding site. The structure contains a well defined UMP molecule in the active site. The binding of UMP involves two sequence segments that are highly conserved among UPRTases. The first segment, Asp131-Ser139, contains the PRPP-binding consensus sequence motif known from other type I phosphoribosyltransferases and binds the ribose-5'-phosphate part of UMP. The second segment, Tyr193-Ala201, which is specific for uracil phosphoribosyltransferases, binds the uracil part of UMP through backbone contacts, partly mediated by a water molecule. Modelling of a PRPP-enzyme complex reveals that uracil can be activated to its tautomeric enol form by the complex. This is consistent with kinetic data, which display ordered sequential binding of substrates, with PRPP binding first. Based on this observation, a reaction mechanism is proposed. |
==About this Structure== | ==About this Structure== | ||
| - | 1I5E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_caldolyticus Bacillus caldolyticus] with U5P 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:// | + | 1I5E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_caldolyticus Bacillus caldolyticus] with <scene name='pdbligand=U5P:'>U5P</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=1I5E OCA]. |
==Reference== | ==Reference== | ||
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[[Category: uracil phosphoribosyltransferase]] | [[Category: uracil phosphoribosyltransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:08:15 2008'' |
Revision as of 11:08, 21 February 2008
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CRYSTAL STRUCTURE OF BACILLUS CALDOLYTICUS URACIL PHOSPHORIBOSYLTRANSFERASE WITH BOUND UMP
Overview
Uracil phosphoribosyltransferase (UPRTase) is part of the salvage pathway that leads to the biosynthesis of UMP. It catalyzes the formation of UMP and pyrophosphate from uracil and alpha-D-5-phosphoribosyl-1-pyrophosphate. Unlike enzymes in the de novo synthesis of UMP, UPRTases have only been found in lower organisms and are therefore potential targets for the development of new antibiotics. UPRTase from Bacillus caldolyticus has been crystallized and the structure has been determined by isomorphous replacement and refined to 3.0 A resolution. UPRTase from B. caldolyticus forms a dimer with the active sites pointing away from each other. A long arm from each subunit wraps around the other subunit, contributing half of the dimer interface. The monomer adopts the phosphoribosyltransferase type I fold, with a small C-terminal hood defining the uracil-binding site. The structure contains a well defined UMP molecule in the active site. The binding of UMP involves two sequence segments that are highly conserved among UPRTases. The first segment, Asp131-Ser139, contains the PRPP-binding consensus sequence motif known from other type I phosphoribosyltransferases and binds the ribose-5'-phosphate part of UMP. The second segment, Tyr193-Ala201, which is specific for uracil phosphoribosyltransferases, binds the uracil part of UMP through backbone contacts, partly mediated by a water molecule. Modelling of a PRPP-enzyme complex reveals that uracil can be activated to its tautomeric enol form by the complex. This is consistent with kinetic data, which display ordered sequential binding of substrates, with PRPP binding first. Based on this observation, a reaction mechanism is proposed.
About this Structure
1I5E is a Single protein structure of sequence from Bacillus caldolyticus with as ligand. Active as Uracil phosphoribosyltransferase, with EC number 2.4.2.9 Full crystallographic information is available from OCA.
Reference
Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding., Kadziola A, Neuhard J, Larsen S, Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6 Pt 2):936-45. Epub, 2002 May 29. PMID:12037295
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