Definition of D-alanine catabolism
As rules and steps, or see full text
Rules
Overview: GapMind describes D-alanine catabolism via D-alanine dehydrogenase, which forms pyruvate. This reaction is part of the MetaCyc pathway for L-alanine catabolism via D-alanine (link). In principle, D-alanine might also be catabolized via racemization to L-alanine and transamination to pyruvate, but this is not described here.
- all: D-alanine-transport and dadA
- D-alanine-transport:
Steps
Pf6N2E2_5402: ABC transporter for D-Alanine, substrate-binding component
Pf6N2E2_5403: ABC transporter for D-Alanine, permease component 2
Pf6N2E2_5404: ABC transporter for D-Alanine, permease component 1
Pf6N2E2_5405: ABC transporter for D-Alanine, ATPase component
AZOBR_RS08235: D-alanine ABC transporter, permease component 1
- Curated sequence AZOBR_RS08235: L-proline and D-alanine ABC transporter, permease component 1
- Comment: An ABC transporter from Azospirillum brasilense, with 5 components, was identified in the fitness data. (Just one component was in the reannotations.) MctP was missed by the clustering tool, but is annotated as transporting D-alanine (see PMC135354, Figure 4A, showing that D-alanine inhibits transport). A related protein, BPHYT_RS22245 (B2T7V3), is involved in D-alanine utilization.
- Total: 1 characterized proteins
AZOBR_RS08240: D-alanine ABC transporter, permease component 2
- UniProt sequence G8ALI9: SubName: Full=Leucine/isoleucine/valine ABC transporter,permease component {ECO:0000313|EMBL:CCC98101.1};
- Total: 1 characterized proteins
AZOBR_RS08245: D-alanine ABC transporter, ATPase component 1
- UniProt sequence G8ALJ0: SubName: Full=Leucine/isoleucine/valine ABC transporter,ATPase component {ECO:0000313|EMBL:CCC98102.1}; EC=3.6.3.- {ECO:0000313|EMBL:CCC98102.1};
- Total: 1 characterized proteins
AZOBR_RS08250: D-alanine ABC transporter, ATPase component 2
- UniProt sequence G8ALJ1: SubName: Full=Leucine//isoleucine/valine ABC transporter,ATPase component {ECO:0000313|EMBL:CCC98103.1}; EC=3.6.3.- {ECO:0000313|EMBL:CCC98103.1};
- Total: 1 characterized proteins
AZOBR_RS08260: D-alanine ABC transporter, substrate-binding component
- UniProt sequence G8ALJ3: SubName: Full=Branched-chain amino acid ABC transporter,substrate-binding periplasmic component {ECO:0000313|EMBL:CCC98105.1};
- Total: 1 characterized proteins
cycA: D-alanine:H+ symporter CycA
- Curated sequence A0A0H2VDI7: D-serine/D-alanine/glycine transporter
- Curated sequence P0AAE0: D-serine/D-alanine/glycine transporter. D-Serine/D-alanine/glycine/D-cycloserine:H+ symporter. D-serine/alanine/glycine/:H+symporter. D-serine/alanine/glycine/:H+symporter
- Curated sequence F2HQ24: Serine transporter, SerP2 or YdgB, of 459 aas and 12 TMSs (Trip et al. 2013). Transports L-alanine (Km = 20 μM), D-alanine (Km = 38 μM), L-serine, D-serine (Km = 356 μM) and glycine (Noens and Lolkema 2015). The encoding gene is adjacent to the one encoding SerP1 (TC# 2.A.3.1.21)
- Curated sequence M1IW84: D-serine/L-alanine/D-alanine/glycine/D-cycloserine uptake porter of 556 aas, CycA
- Curated sequence GFF1065: L-alanine and D-alanine permease
- Curated sequence AO353_16120: D-alanine and L-alanine transporter
- Curated sequence AO356_17670: L-alanine and D-alanine permease
- Curated sequence A2RI86: DL-alanine permease SerP2
- Total: 8 characterized proteins
mctP: D-alanine transporter MctP
- Curated sequence Q8VM88: The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine)
- Curated sequence Q1M7A2: Monocarboxylate transport permease protein
- UniProt sequence B2T7V3: SubName: Full=Na+/solute symporter {ECO:0000313|EMBL:ACD18855.1};
- Total: 3 characterized proteins
dadA: D-alanine dehydrogenase
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About GapMind
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory