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4u8m

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Revision as of 19:53, 5 August 2016

Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant Y317A

Structural highlights

4u8m is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4u8i, 4u8j, 4u8k, 4u8l, 4u8n, 4u8o, 4u8p
Activity:	UDP-galactopyranose mutase, with EC number 5.4.99.9
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

UDP-galactopyranose mutase (UGM) catalyzes the interconversion between UDP-galactopyranose and UDP-galactofuranose. Absent in humans, galactofuranose is found in bacterial and fungal cell walls and is a cell surface virulence factor in protozoan parasites. For these reasons, UGMs are targets for drug discovery. Here, we report a mutagenesis and structural study of the UGMs from Aspergillus fumigatus and Trypanosoma cruzi focused on active site residues that are conserved in eukaryotic UGMs but are absent or different in bacterial UGMs. Kinetic analysis of the variants F66A, Y104A, Q107A, N207A, and Y317A (A. fumigatus numbering) show decreases in kcat/KM values of 200-1000-fold for the mutase reaction. In contrast, none of the mutations significantly affect the kinetics of enzyme activation by NADPH. These results indicate that the targeted residues are important for promoting the transition state conformation for UDP-galactofuranose formation. Crystal structures of the A. fumigatus mutant enzymes were determined in the presence and absence of UDP to understand the structural consequences of the mutations. The structures suggest important roles for Asn207 in stabilizing the closed active site, and Tyr317 in positioning of the uridine ring. Phe66 and the corresponding residue in Mycobacterium tuberculosis UGM (His68) play a role as the backstop, stabilizing the galactopyranose group for nucleophilic attack. Together, these results provide insight into the essentiality of the targeted residues for realizing maximal catalytic activity and a proposal for how conformational changes that close the active site are temporally related and coupled together.

Contributions of Unique Active Site Residues of Eukaryotic UDP-Galactopyranose Mutases to Substrate Recognition and Active Site Dynamics.,Da Fonseca I, Qureshi IA, Mehra-Chaudhary R, Kizjakina K, Tanner JJ, Sobrado P Biochemistry. 2014 Dec 2. PMID:25412209^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Da Fonseca I, Qureshi IA, Mehra-Chaudhary R, Kizjakina K, Tanner JJ, Sobrado P. Contributions of Unique Active Site Residues of Eukaryotic UDP-Galactopyranose Mutases to Substrate Recognition and Active Site Dynamics. Biochemistry. 2014 Dec 2. PMID:25412209 doi:http://dx.doi.org/10.1021/bi501008z

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u8m"

@@ Line 1: / Line 1: @@
 ==Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant Y317A==
 <StructureSection load='4u8m' size='340' side='right' caption='[[4u8m]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u8i|4u8i]], [[4u8j|4u8j]], [[4u8k|4u8k]], [[4u8l|4u8l]], [[4u8n|4u8n]], [[4u8o|4u8o]], [[4u8p|4u8p]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-galactopyranose_mutase UDP-galactopyranose mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.9 5.4.99.9] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u8m RCSB], [http://www.ebi.ac.uk/pdbsum/4u8m PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8m OCA], [http://pdbe.org/4u8m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u8m RCSB], [http://www.ebi.ac.uk/pdbsum/4u8m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u8m ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u8m" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[UDP-galactopyranose mutase|UDP-galactopyranose mutase]]
 == References ==
 <references/>

4u8m

From Proteopedia

Revision as of 19:53, 5 August 2016

Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant Y317A

Structural highlights

Publication Abstract from PubMed

See Also

References

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