2m80

From Proteopedia

(Difference between revisions)

Revision as of 22:43, 9 August 2018

Solution structure of yeast dithiol glutaredoxin Grx8

Structural highlights

2m80 is a 1 chain structure with sequence from Baker's yeast. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	GRX8 (Baker's yeast)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GLRX8_YEAST] Glutathione-dependent oxidoreductase with lower activity compared to the other members of the glutaredoxin family. The disulfide bond functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase.^[1] ^[2]

Publication Abstract from PubMed

Glutaredoxins (Grxs) are wide-spread oxidoreductases that are found in all kingdoms of life. The yeast Saccharomyces cerevisiae encodes eight Grxs, among which, Grx8 shares a sequence identity of 30 and 23% with typical dithiol Grx1 and Grx2, respectively, but it exhibits a much lower GSH-dependent oxidoreductase activity. To elucidate its catalytic mechanism, we solved the solution structure of Grx8, which displays a typical Grx fold. Structural analysis indicated that Grx8 possesses a negatively charged CXXC motif (Cys(33)-Pro(34)-Asp(35)-Cys(36)) and a GSH-recognition site, which are distinct from Grx1 and Grx2. Subsequent structure-guided site mutations revealed that the D35Y single mutant and N80T/L81V double mutant possess increased activity of 10- and 11-fold, respectively; moreover, the D35Y/N80T/L81V triple mutant has increased activity of up to 44-fold, which is comparable to that of canonical Grx. Biochemical analyses suggested that the increase in catalytic efficiency resulted from a decreased pKa value of catalytic cysteine Cys33 and/or enhancement of the putative GSH-recognition site. Moreover, NMR chemical shift perturbation analyses combined with GSH analogue inhibition assays enabled us to elucidate that wild-type Grx8 and all mutants adopt a ping-pong mechanism of catalysis. All together, these findings provide structural insights into the catalytic mechanism of dithiol Grxs.

Structure-guided activity enhancement and catalytic mechanism of yeast grx8.,Tang Y, Zhang J, Yu J, Xu L, Wu J, Zhou CZ, Shi Y Biochemistry. 2014 Apr 8;53(13):2185-96. doi: 10.1021/bi401293s. Epub 2014 Mar, 25. PMID:24611845^[3]

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

References

↑ Mesecke N, Spang A, Deponte M, Herrmann JM. A novel group of glutaredoxins in the cis-Golgi critical for oxidative stress resistance. Mol Biol Cell. 2008 Jun;19(6):2673-80. doi: 10.1091/mbc.E07-09-0896. Epub 2008, Apr 9. PMID:18400945 doi:http://dx.doi.org/10.1091/mbc.E07-09-0896
↑ Eckers E, Bien M, Stroobant V, Herrmann JM, Deponte M. Biochemical characterization of dithiol glutaredoxin 8 from Saccharomyces cerevisiae: the catalytic redox mechanism redux. Biochemistry. 2009 Feb 17;48(6):1410-23. doi: 10.1021/bi801859b. PMID:19166312 doi:http://dx.doi.org/10.1021/bi801859b
↑ Tang Y, Zhang J, Yu J, Xu L, Wu J, Zhou CZ, Shi Y. Structure-guided activity enhancement and catalytic mechanism of yeast grx8. Biochemistry. 2014 Apr 8;53(13):2185-96. doi: 10.1021/bi401293s. Epub 2014 Mar, 25. PMID:24611845 doi:http://dx.doi.org/10.1021/bi401293s

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m80"

@@ Line 1: / Line 1: @@
 ==Solution structure of yeast dithiol glutaredoxin Grx8==
 <StructureSection load='2m80' size='340' side='right' caption='[[2m80]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m80]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M80 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m80]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M80 FirstGlance]. <br>
-</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=2m80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m80 OCA], [http://pdbe.org/2m80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m80 RCSB], [http://www.ebi.ac.uk/pdbsum/2m80 PDBsum]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRX8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=2m80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m80 OCA], [http://pdbe.org/2m80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m80 RCSB], [http://www.ebi.ac.uk/pdbsum/2m80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2m80 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Baker's yeast]]
 [[Category: Shi, Y]]
 [[Category: Tang, Y]]

2m80

From Proteopedia

Revision as of 22:43, 9 August 2018

Solution structure of yeast dithiol glutaredoxin Grx8

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox