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4u8i

From Proteopedia

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Current revision

Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant F66A

Structural highlights

4u8i is a 4 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q4W1X2_ASPFM

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 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u8i"

Categories: Aspergillus fumigatus | Large Structures | Chaudhary R | Qureshi IA | Tanner JJ

@@ Line 1: / Line 1: @@
 ==Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant F66A==
-<StructureSection load='4u8i' size='340' side='right' caption='[[4u8i]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
+<StructureSection load='4u8i' size='340' side='right'caption='[[4u8i]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u8i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U8I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u8i]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U8I FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u8j|4u8j]], [[4u8k|4u8k]], [[4u8l|4u8l]], [[4u8m|4u8m]], [[4u8n|4u8n]], [[4u8o|4u8o]], [[4u8p|4u8p]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4u8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8i OCA], [https://pdbe.org/4u8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u8i RCSB], [https://www.ebi.ac.uk/pdbsum/4u8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u8i ProSAT]</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=4u8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8i OCA], [http://pdbe.org/4u8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u8i RCSB], [http://www.ebi.ac.uk/pdbsum/4u8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u8i ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q4W1X2_ASPFM Q4W1X2_ASPFM]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 ==See Also==
-*[[UDP-galactopyranose mutase|UDP-galactopyranose mutase]]
+*[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: UDP-galactopyranose mutase]]
+[[Category: Aspergillus fumigatus]]
-[[Category: Chaudhary, R]]
+[[Category: Large Structures]]
-[[Category: Qureshi, I A]]
+[[Category: Chaudhary R]]
-[[Category: Tanner, J J]]
+[[Category: Qureshi IA]]
-[[Category: Flavin adenine dinucleotide binding]]
+[[Category: Tanner JJ]]
-[[Category: Isomerase]]
-[[Category: Mutase]]
-[[Category: Nucleotide binding]]

4u8i

From Proteopedia

Current revision

Structure of Aspergillus fumigatus UDP-Galactopyranose mutase mutant F66A

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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