4opc

From Proteopedia

(Difference between revisions)

Current revision

Constructing tailored isoprenoid products by structure-guided modification of geranylgeranyl reductase.

Structural highlights

4opc is a 1 chain structure with sequence from Sulfolobus acidocaldarius DSM 639. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GGR_SULAC Is involved in the reduction of 2,3-digeranylgeranylglycerophospholipids (unsaturated archaeols) into 2,3-diphytanylglycerophospholipids (saturated archaeols) in the biosynthesis of archaeal membrane lipids. Catalyzes the formation of archaetidic acid (2,3-di-O-phytanyl-sn-glyceryl phosphate) from 2,3-di-O-geranylgeranylglyceryl phosphate (DGGGP) via the hydrogenation of each double bond of the isoprenoid chains. Is not active with NADPH or NADH as an electron donor; the physiological reducing agent is unknown. Is also active on the more upstream precursors of membrane lipid biosynthesis, catalyzing the complete reduction of 3-O-geranylgeranylglyceryl phosphate (GGGP) to 3-O-phytanylglyceryl phosphate, and the partial reduction of geranylgeranyl diphosphate (GGPP) to phytyl diphosphate, thus reducing three of four GGPP double bonds and preserving the allylic double bond (at position 2). This reaction product is a reactive prenyl donor, which can be used as a substrate by archaeal prenyltransferases such as GGGP synthases.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The archaeal enzyme geranylgeranyl reductase (GGR) catalyzes hydrogenation of carbon-carbon double bonds to produce the saturated alkyl chains of the organism's unusual isoprenoid-derived cell membrane. Enzymatic reduction of isoprenoid double bonds is of considerable interest both to natural products researchers and to synthetic biologists interested in the microbial production of isoprenoid drug or biofuel molecules. Here we present crystal structures of GGR from Sulfolobus acidocaldarius, including the structure of GGR bound to geranylgeranyl pyrophosphate (GGPP). The structures are presented alongside activity data that depict the sequential reduction of GGPP to H6GGPP via the intermediates H2GGPP and H4GGPP. We then modified the enzyme to generate sequence variants that display increased rates of H6GGPP production or are able to halt the extent of reduction at H2GGPP and H4GGPP. Crystal structures of these variants not only reveal the structural bases for their altered activities; they also shed light onto the catalytic mechanism employed.

Constructing Tailored Isoprenoid Products by Structure-Guided Modification of Geranylgeranyl Reductase.,Kung Y, McAndrew RP, Xie X, Liu CC, Pereira JH, Adams PD, Keasling JD Structure. 2014 Jun 17. pii: S0969-2126(14)00148-8. doi:, 10.1016/j.str.2014.05.007. PMID:24954619^[4]

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

References

↑ Sato S, Murakami M, Yoshimura T, Hemmi H. Specific partial reduction of geranylgeranyl diphosphate by an enzyme from the thermoacidophilic archaeon Sulfolobus acidocaldarius yields a reactive prenyl donor, not a dead-end product. J Bacteriol. 2008 Jun;190(11):3923-9. doi: 10.1128/JB.00082-08. Epub 2008 Mar 28. PMID:18375567 doi:http://dx.doi.org/10.1128/JB.00082-08
↑ Sasaki D, Fujihashi M, Iwata Y, Murakami M, Yoshimura T, Hemmi H, Miki K. Structure and mutation analysis of archaeal geranylgeranyl reductase. J Mol Biol. 2011 Jun 17;409(4):543-57. Epub 2011 Apr 16. PMID:21515284 doi:http://dx.doi.org/10.1016/j.jmb.2011.04.002
↑ Kung Y, McAndrew RP, Xie X, Liu CC, Pereira JH, Adams PD, Keasling JD. Constructing Tailored Isoprenoid Products by Structure-Guided Modification of Geranylgeranyl Reductase. Structure. 2014 Jun 17. pii: S0969-2126(14)00148-8. doi:, 10.1016/j.str.2014.05.007. PMID:24954619 doi:http://dx.doi.org/10.1016/j.str.2014.05.007
↑ Kung Y, McAndrew RP, Xie X, Liu CC, Pereira JH, Adams PD, Keasling JD. Constructing Tailored Isoprenoid Products by Structure-Guided Modification of Geranylgeranyl Reductase. Structure. 2014 Jun 17. pii: S0969-2126(14)00148-8. doi:, 10.1016/j.str.2014.05.007. PMID:24954619 doi:http://dx.doi.org/10.1016/j.str.2014.05.007

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/4opc"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4opc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sulfolobus_acidocaldarius_DSM_639 Sulfolobus acidocaldarius DSM 639]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OPC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=PGT:(1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL+STEARATE'>PGT</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]] 1.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=PGT:(1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL+STEARATE'>PGT</scene></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=4opc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4opc OCA], [https://pdbe.org/4opc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4opc RCSB], [https://www.ebi.ac.uk/pdbsum/4opc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4opc ProSAT]</span></td></tr>
 </table>

4opc

From Proteopedia

Current revision

Constructing tailored isoprenoid products by structure-guided modification of geranylgeranyl reductase.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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