Rv0116c (ldtA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: hypothetical protein
- PATRIC: Possible membrane protein
- TUBERCULIST: Probable LD-transpeptidase LdtA
- NCBI: Probable L,D-transpeptidase LdtA
- updated information (H37Rv4):
  - gene name: ldtA
  - function: (3,3-) L,D-transpeptidase, peptidoglycan synthesis
  - reference: Cordillot (2013) PMC3837840
Coordinates in H37Rv: 140267 - 141022
Gene length: 756 bp (with stop codon), 251 aa (without stop codon)
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0071972 - peptidoglycan L,D-transpeptidase activity (Uniprot)
- GO:0071555 - cell wall organization (Uniprot)
- GO:0042597 - periplasmic space (Uniprot)
- GO:0018104 - peptidoglycan-protein cross-linking (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009252 - peptidoglycan biosynthetic process (Uniprot)
- GO:0008360 - regulation of cell shape (Uniprot)
- GO:0006508 - proteolysis (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
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:
Search for Latest Homologs in PDB

Top 10 Homologs in PDB (as of Apr 2026):

PDB	aa ident	species	PDB title
5E5L	100%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom
5E51	100%	Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)	Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct
4JMX	100%	Mycobacterium tuberculosis	Structure of LD transpeptidase LdtMt1 in complex with imipenem
4JMN	100%	Mycobacterium tuberculosis	Crystal structure of LD transpeptidase LdtMt1 from M. tuberculosis
4XVO	64%	Mycobacterium smegmatis	L,D-transpeptidase from Mycobacterium smegmatis
6D51	50%	Mycobacterium tuberculosis	Crystal structure of L,D-transpeptidase 3 from Mycobacterium tuberculosis in complex with a faropenem-derived adduct
6D4K	50%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of L,D-transpeptidase 3 from Mycobacterium tuberculosis at 1.32 A resolution
4K73	50%	Mycobacterium tuberculosis	X-ray crystal structure of an L,D-transpeptidase from Mycobacterium tuberculosis H37Rv
8PXZ	43%	Mycobacterium tuberculosis	Crystal structure of the transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with natural substrate
8J65	43%	Mycobacterium tuberculosis	the structure of L,D-transpeptidase LdtMt2 complex with citrate

Links to additional information on ldtA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.774 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRRVVRYLSVVVAITLMLTAESVSIATAAVPPLQPIPGVASVSPANGAVVGVAHPVVVTFTTPVTDRRAVERSIRISTPHNTTGHFEWVASNVVRWVPHR
YWPPHTRVSVGVQELTEGFETGDALIGVASISAHTFTVSRNGEVLRTMPASLGKPSRPTPIGSFHAMSKERTVVMDSRTIGIPLNSSDGYLLTAHYAVRV
TWSGVYVHSAPWSVNSQGYANVSHGCINLSPDNAAWYFDAVTVGDPIEVVG

(Nucleotide sequence available on KEGG)

Additional Information

LdtMt1/LdtA, (3,3-) L,D-transpeptidase, peptidoglycan synthesis
http://jb.asm.org/content/190/12/4360
Dubee et al (2012). AAC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421625/

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv0116c/ldtA, gene len: 755 bp, num TA sites: 18

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.09)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.084)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-0.54)	YM rich vs minimal medium	resampling

Analysis of Positive Selection in Clinical Isolates new

data from Culviner et al (2025) (55,259 Mtb clinical isolates)
- overall pN/pS for Rv0116c: 0.680423206
- lineage-specific pN/pS in L1: 1.151485426
- lineage-specific pN/pS in L2: 0.588536996
- lineage-specific pN/pS in L3: 0.575742713
- lineage-specific pN/pS in L4: 0.593189462

Analysis of dN/dS (omega) in a global collection of 10k Mtb clinical isolates using GenomegaMap (Window model)
clinical isolates collection: global set of 10,626 Mtb genomes
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	global set of 10,626 Mtb clinical isolates
under significant positive selection?	NO
omega peak height (95%CI lower bound)	1.01 (0.51)
codons under selection
omega plots
genetic variants*	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

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: see table of TFOE interactions below

Interactions based on ChIPSeq data

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv3416 (whiB3)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0967 (csoR) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3246c (mtrA) (Direct binding)

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

TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01

gene	dysregulated by OE of	LFC
Rv0116c/ldtA	Rv3416/whiB3	1.19

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3416 (whiB3)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	Comment
Interaction	RegulatedBy Rv0757	yamir.moreno	IEP	Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv2711	yamir.moreno	IEP	Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Symbol	ldtA	mjackson	IDA	Peptidoglycan assembly/maturation
Name	L,D-transpeptidase	mjackson	IDA	Peptidoglycan assembly/maturation

TB Genome Annotation Portal