Rv2870c (dxr)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 1-deoxy-D-xylulose 5-phosphate reductoisomerase
- REFSEQ: 1-deoxy-D-xylulose 5-phosphate reductoisomerase
- PATRIC: 1-deoxy-D-xylulose 5-phosphate reductoisomerase (EC 1.1.1.267)
- TUBERCULIST: Probable 1-deoxy-D-xylulose 5-phosphate reductoisomerase Dxr (DXP reductoisomerase) (1-deoxyxylulose-5-phosphate reductoisomerase)
- NCBI: Probable 1-deoxy-D-xylulose 5-phosphate reductoisomerase Dxr (DXP reductoisomerase) (1-deoxyxylulose-5-phosphate reductoisomerase)
- updated information (H37Rv4):
  - gene name: dxr
  - function:
  - reference:
Type: Not Target
Start: 3181770
End: 3183011
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0070402 - NADPH binding (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0051484 - isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway involved in terpenoid biosynthetic process (Uniprot)
- GO:0051483 - terpenoid biosynthetic process, mevalonate-independent (Uniprot)
- GO:0050897 - cobalt ion binding (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0030604 - 1-deoxy-D-xylulose-5-phosphate reductoisomerase activity (Uniprot)
- GO:0030145 - manganese ion binding (Uniprot)
- GO:0019288 - isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0008299 - isoprenoid biosynthetic process (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NADPH[c] + DX5P[c] -> NADP[c] + MDE4P[c]
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 4aic, 2jcz, 2jcx, 2jcy, 2jcv, 2y1f, 2y1e, 2y1d, 2y1c, 2y1g, 3ras, 2jd2, 2jd1, 2jd0, 2c82, 4a03
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
4AIC	100%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with fosmidomycin, manganese and NADPH
4A03	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal Structure of Mycobacterium tuberculosis DXR in complex with the antibiotic FR900098 and cofactor NADPH
3ZI0	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of Mycobacterium tuberculosis DXR in complex with a fosmidomycin analogue
3ZHZ	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of Mycobacterium tuberculosis DXR in complex with a fosmidomycin analogue
3ZHY	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of Mycobacterium tuberculosis DXR in complex with a di- substituted fosmidomycin analogue
3ZHX	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of Mycobacterium tuberculosis DXR in complex with a fosmidomycin analogue
3RAS	100%	Mycobacterium tuberculosis	Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with a lipophilic phosphonate inhibitor
2Y1G	100%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with a 3,4- dichlorophenyl-substituted FR900098 analogue and manganese.
2Y1F	100%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with a 3,4- dichlorophenyl-substituted fosmidomycin analogue, manganese and NADPH.
2Y1E	100%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, DXR, Rv2870c, from Mycobacterium tuberculosis, in complex with manganese.

Links to additional information on dxr:
- KEGG - nucleotide and amino acid sequences of gene
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -7.048 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTNSTDGRADGRLRVVVLGSTGSIGTQALQVIADNPDRFEVVGLAAGGAHLDTLLRQRAQTGVTNIAVADEHAAQRVGDIPYHGSDAATRLVEQTEADVV
LNALVGALGLRPTLAALKTGARLALANKESLVAGGSLVLRAARPGQIVPVDSEHSALAQCLRGGTPDEVAKLVLTASGGPFRGWSAADLEHVTPEQAGAH
PTWSMGPMNTLNSASLVNKGLEVIETHLLFGIPYDRIDVVVHPQSIIHSMVTFIDGSTIAQASPPDMKLPISLALGWPRRVSGAAAACDFHTASSWEFEP
LDTDVFPAVELARQAGVAGGCMTAVYNAANEEAAAAFLAGRIGFPAIVGIIADVLHAADQWAVEPATVDDVLDAQRWARERAQRAVSGMASVAIASTAKP
GAAGRHASTLERS

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.997400; 12 non-insertions in a row out of 16 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999950; 13 non-insertions in a row out of 16 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999950; 13 non-insertions in a row out of 16 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 14 non-insertions in a row out of 16 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 14 non-insertions in a row out of 16 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.25
Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0135c (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto Proc. Natl. Acad. Sci. U.S.A. 1998	njamshidi	IDA	9707569\|15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - IDA	njamshidi	IDA	15065882	see PMID: 15065882 and PMID: 9707569 authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 1998
Citation	Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. A. Argyrou & JS. Blanchard Biochemistry 2004	njamshidi	ISS	15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - ISS	njamshidi	ISS	15065882	see PMID: 15065882 and PMID: 9707569 A. Argyrou & JS. Blanchard Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. Biochemistry 2004
Citation	A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto Proc. Natl. Acad. Sci. U.S.A. 1998	njamshidi	ISS	9707569\|15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - ISS	njamshidi	ISS	15065882	see PMID: 15065882 and PMID: 9707569 authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 1998
Citation	Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. A. Argyrou & JS. Blanchard Biochemistry 2004	njamshidi	IPI	15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - IPI	njamshidi	IPI	15065882	see PMID: 15065882 and PMID: 9707569 A. Argyrou & JS. Blanchard Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. Biochemistry 2004
Citation	A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto Proc. Natl. Acad. Sci. U.S.A. 1998	njamshidi	IPI	9707569\|15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - IPI	njamshidi	IPI	15065882	see PMID: 15065882 and PMID: 9707569 authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 1998
Citation	Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. A. Argyrou & JS. Blanchard Biochemistry 2004	njamshidi	IDA	15065882	see PMID: 15065882 and PMID: 9707569
Term	TBRXN:DXPRIi 1-deoxy-D-xylulose reductoisomerase - IDA	njamshidi	IDA	15065882	see PMID: 15065882 and PMID: 9707569 A. Argyrou & JS. Blanchard Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. Biochemistry 2004
Symbol	ispC	mjackson	IDA		Non-mevalonate isopentenyl diphosphate synthesis
Name	1-deoxy-D-xylulose 5-phosphate reductoisomerase	mjackson	IDA		Non-mevalonate isopentenyl diphosphate synthesis
Citation	A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto Proc. Natl. Acad. Sci. U.S.A. 1998	jjmcfadden		9707569	Inferred from direct assay
Term	EC:1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase. - NR	jjmcfadden	NR		Inferred from direct assay authors,S. Takahashi,T. Kuzuyama,H. Watanabe,H. Seto A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 1998

TB Genome Annotation Portal