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4xt6

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Revision as of 17:51, 26 April 2023

Crystal structure of Rv2671 from Mycobacterium tuberculosis in complex with the tetrahydropteridine ring of tetrahydrofolate (THF)

Structural highlights

4xt6 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P71968_MYCTU

Publication Abstract from PubMed

Mycobacterium tuberculosis (Mtb) Rv2671 is annotated as a 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate (AROPP) reductase (RibD) in the riboflavin biosynthetic pathway. Recently, a strain of Mtb with a mutation in the 5' untranslated region of Rv2671, which resulted in its overexpression, was found to be resistant to dihydrofolate reductase (DHFR) inhibitors including the anti-Mtb drug para-aminosalicylic acid (PAS). In this study, a biochemical analysis of Rv2671 showed that it was able to catalyze the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), which explained why the overexpression of Rv2671 was sufficient to confer PAS resistance. We solved the structure of Rv2671 in complex with the NADP(+) and tetrahydrofolate (THF), which revealed the structural basis for the DHFR activity. The structures of Rv2671 complexed with two DHFR inhibitors, trimethoprim and trimetrexate, provided additional details of the substrate binding pocket and elucidated the differences between their inhibitory activities. Finally, Rv2671 was unable to catalyze the reduction of AROPP, which indicated that Rv2671 and its closely related orthologues are not involved in riboflavin biosynthesis.

Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance.,Cheng YS, Sacchettini JC Biochemistry. 2016 Feb 23;55(7):1107-19. doi: 10.1021/acs.biochem.5b00993. Epub, 2016 Feb 5. PMID:26848874^[1]

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

References

↑ Cheng YS, Sacchettini JC. Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance. Biochemistry. 2016 Feb 23;55(7):1107-19. doi: 10.1021/acs.biochem.5b00993. Epub, 2016 Feb 5. PMID:26848874 doi:http://dx.doi.org/10.1021/acs.biochem.5b00993

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/4xt6"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Cheng YS | Sacchettini JC

@@ Line 3: / Line 3: @@
 <StructureSection load='4xt6' size='340' side='right'caption='[[4xt6]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xt6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XT6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xt6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XT6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=44V:(6S)-2-AMINO-6-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-4(3H)-ONE'>44V</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=44V:(6S)-2-AMINO-6-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-4(3H)-ONE'>44V</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xrb|4xrb]], [[4xt5|4xt5]], [[4xt8|4xt8]], [[4xt7|4xt7]], [[4xt4|4xt4]]</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=4xt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt6 OCA], [https://pdbe.org/4xt6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xt6 RCSB], [https://www.ebi.ac.uk/pdbsum/4xt6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt6 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ribD, Rv2671, RVBD_2671, LH57_14640, P425_02787 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=4xt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt6 OCA], [http://pdbe.org/4xt6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xt6 RCSB], [http://www.ebi.ac.uk/pdbsum/4xt6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt6 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/P71968_MYCTU P71968_MYCTU]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Cheng, Y S]]
+[[Category: Cheng YS]]
-[[Category: Sacchettini, J C]]
+[[Category: Sacchettini JC]]
-[[Category: Structural genomic]]
-[[Category: Nadp+]]
-[[Category: Oxidoreductase]]
-[[Category: Reductase]]
-[[Category: Tbsgc]]

4xt6

From Proteopedia

Revision as of 17:51, 26 April 2023

Crystal structure of Rv2671 from Mycobacterium tuberculosis in complex with the tetrahydropteridine ring of tetrahydrofolate (THF)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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