8bgr: Difference between revisions
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==FAD-independent Methylene-Tetrahydrofolate Reductase from Mycobacterium hassiacum== | |||
<StructureSection load='8bgr' size='340' side='right'caption='[[8bgr]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8bgr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_hassiacum Mycolicibacterium hassiacum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BGR FirstGlance]. <br> | |||
</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=8bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bgr OCA], [https://pdbe.org/8bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bgr RCSB], [https://www.ebi.ac.uk/pdbsum/8bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bgr ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/K5BDY6_MYCHD K5BDY6_MYCHD] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
FAD-independent methylene-tetrahydrofolate (methylene-H(4) F) reductase (Mfr), recently identified in mycobacteria, catalyzes the reduction of methylene-H(4) F to methyl-H(4) F with NADH as hydride donor by a ternary complex mechanism. This biochemical reaction corresponds to that of the ubiquitous FAD-dependent methylene-H(4) F reductase (MTHFR), although the latter uses a ping-pong mechanism with the prosthetic group as intermediate hydride carrier. Comparative genomics and genetic analyses indicated that Mfr is indispensable for the growth of Mycobacterium tuberculosis, which lacks the MTHFR encoding gene. Therefore, Mfr appears to be an excellent target for the design of antimycobacterial drugs. Here, we report the heterologous production, enzymological characterization, and the crystal structure of Mfr from the thermophilic mycobacterium Mycobacterium hassiacum (hMfr), which shows 78% sequence identity to Mfr from M. tuberculosis. Although hMfr and MTHFR have minor sequence identity and different catalytic mechanisms, their structures are highly similar, thus suggesting a divergent evolution of Mfr and MTHFR from a common ancestor. Most of the important active site residues of MTHFR are conserved and equivalently positioned in the tertiary structure of hMfr. The Glu9Gln variant of hMfr exhibits a drastic reduction of the catalytic activity, which supports the predicted function of the glutamate residue as proton donor in both hMfr and MTHFR. Thus, highly similar binding modes for the C(1) -carriers and the reducing agents in hMfr and MTHFR are assumed. | |||
Crystal structure of FAD-independent methylene-tetrahydrofolate reductase from Mycobacterium hassiacum.,Gehl M, Demmer U, Ermler U, Shima S Proteins. 2023 Apr 29. doi: 10.1002/prot.26504. PMID:37119125<ref>PMID:37119125</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8bgr" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium hassiacum]] | |||
[[Category: Ermler U]] | |||
[[Category: Gehl M]] | |||
[[Category: Shima S]] | |||
Revision as of 09:51, 10 May 2023
FAD-independent Methylene-Tetrahydrofolate Reductase from Mycobacterium hassiacumFAD-independent Methylene-Tetrahydrofolate Reductase from Mycobacterium hassiacum
Structural highlights
FunctionPublication Abstract from PubMedFAD-independent methylene-tetrahydrofolate (methylene-H(4) F) reductase (Mfr), recently identified in mycobacteria, catalyzes the reduction of methylene-H(4) F to methyl-H(4) F with NADH as hydride donor by a ternary complex mechanism. This biochemical reaction corresponds to that of the ubiquitous FAD-dependent methylene-H(4) F reductase (MTHFR), although the latter uses a ping-pong mechanism with the prosthetic group as intermediate hydride carrier. Comparative genomics and genetic analyses indicated that Mfr is indispensable for the growth of Mycobacterium tuberculosis, which lacks the MTHFR encoding gene. Therefore, Mfr appears to be an excellent target for the design of antimycobacterial drugs. Here, we report the heterologous production, enzymological characterization, and the crystal structure of Mfr from the thermophilic mycobacterium Mycobacterium hassiacum (hMfr), which shows 78% sequence identity to Mfr from M. tuberculosis. Although hMfr and MTHFR have minor sequence identity and different catalytic mechanisms, their structures are highly similar, thus suggesting a divergent evolution of Mfr and MTHFR from a common ancestor. Most of the important active site residues of MTHFR are conserved and equivalently positioned in the tertiary structure of hMfr. The Glu9Gln variant of hMfr exhibits a drastic reduction of the catalytic activity, which supports the predicted function of the glutamate residue as proton donor in both hMfr and MTHFR. Thus, highly similar binding modes for the C(1) -carriers and the reducing agents in hMfr and MTHFR are assumed. Crystal structure of FAD-independent methylene-tetrahydrofolate reductase from Mycobacterium hassiacum.,Gehl M, Demmer U, Ermler U, Shima S Proteins. 2023 Apr 29. doi: 10.1002/prot.26504. PMID:37119125[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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