Gene Rv3465 (rfbC)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in dTDP-L-rhamnose biosynthesis, within the O antigen biosynthesis pathway of lipopolysaccharide biosynthesis: conversion of dTDP-4-keto-6-deoxy-D-glucose to dTDP-4-keto-rhamnose [catalytic activity: dTDP-4-dehydro-6-deoxy-D-glucose = dTDP-4-dehydro-6-deoxy-L-mannose]. |
| Product | dTDP-4-dehydrorhamnose 3,5-epimerase RmlC (dTDP-4-keto-6-deoxyglucose 3,5-epimerase) (dTDP-L-rhamnose synthetase) (thymidine diphospho-4-keto-rhamnose 3,5-epimerase) |
| Comments | Rv3465, (MTCY13E12.18), len: 202 aa. RmlC (alternate gene name: rfbC), dTDP-4-dehydrorhamnose 3,5-epimerase (see citations below), nearly identical to O33170|RMLC RMLC protein from Mycobacterium tuberculosis (203 aa), FASTA scores: opt: 1171, E(): 2.6e-71, (89.5% identity in 200 aa overlap) (previously known as rfbC). Equivalent to Q9X7A4|RMLC|ML1965 putative dTDP-4-dehydrorhamnose 3,5-epimerase from Mycobacterium leprae (202 aa), FASTA scores: opt: 1072, E(): 1.1e-64, (75.4% identity in 199 aa overlap). Also highly similar to others e.g. Q9F8S7|CUMY from Streptomyces rishiriensis (198 aa), FASTA scores: opt: 671, E(): 7e-38, (51.3% identity in 193 aa overlap); Q9L6C5 from Streptomyces antibioticus (202 aa), FASTA scores: opt: 665, E(): 1.8e-37, (49.25% identity in 197 aa overlap); P29783|STRM_STRGR from Streptomyces griseus (200 aa), FASTA scores: opt: 608, E(): 1.2e-33, (49.25% identity in 201 aa overlap); Q54265|STRM from Streptomyces glaucescens (200 aa), FASTA scores: opt: 603, E(): 2.5e-33, (46.7% identity in 197 aa overlap); etc. Also highly similar to Q9S4D4|TYLJ putative NDP-hexose 3-epimerase from Streptomyces fradiae (205 aa), FASTA scores: opt: 625, E(): 8.6e-35, (45.9% identity in 194 aa overlap). |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | Identified by mass spectrometry in Triton X-114 extracts of M. tuberculosis H37Rv (See Malen et al., 2010). Identified by mass spectrometry in the culture filtrate, membrane protein fraction, and whole cell lysates of M. tuberculosis H37Rv (See de Souza et al., 2011). |
| Transcriptomics | mRNA identified by microarray analysis and down-regulated after 24h and 96h of starvation (see Betts et al., 2002). |
| Mutant | Essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Essential gene by Himar1 transposon mutagenesis in H37Rv strain (see Sassetti et al., 2003). Essential gene for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). M. smegmatis knockout shows rmlC is essential for growth (See Li et al., 2006). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 3882834 | 3883442 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv3465|rmlC
MKARELDVPGAWEITPTIHVDSRGLFFEWLTDHGFRAFAGHSLDVRQVNCSVSSAGVLRGLHFAQLPPSQAKYVTCVSGSVFDVVVDIREGSPTFGRWDSVLLDDQDRRTIYVSEGLAHGFLALQDNSTVMYLCSAEYNPQREHTICATDPTLAVDWPLVDGAAPSLSDRDAAAPSFEDVRASGLLPRWEQTQRFIGEMRGT
Bibliography
- Stern RJ et al. [1999]. Conversion of dTDP-4-keto-6-deoxyglucose to free dTDP-4-keto-rhamnose by the rmIC gene products of Escherichia coli and Mycobacterium tuberculosis. Product Biochemistry Function
- Giraud MF et al. [1999]. Purification, crystallization and preliminary structural studies of dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase (RmlC), the third enzyme of the dTDP-L-rhamnose synthesis pathway, from Salmonella enterica serovar typhimurium. Homolog Product Structure
- Belanger AE and Inamine JM [2000]. Review
- Ma Y, Stern RJ, Scherman MS, Vissa VD, Yan W, Jones VC, Zhang F, Franzblau SG, Lewis WH and McNeil MR [2001]. Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose. Product Biochemistry Function
- Betts JC et al. [2002]. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Transcriptome
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Babaoglu K et al. [2003]. Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Structure
- Kantardjieff KA et al. [2004]. Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway. Structure
- Li W et al. [2006]. rmlB and rmlC genes are essential for growth of mycobacteria. Mutant
- Dong C et al. [2007]. RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation. Structure
- Målen H et al. [2010]. Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. Proteomics
- Griffin JE et al. [2011]. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. Mutant
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
