Finding step leuA for L-leucine biosynthesis in Desulforamulus ruminis DSM 2154
5 candidates for leuA: 2-isopropylmalate synthase
Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway
GapMind searches the predicted proteins for candidates by using ublast (a fast alternative to protein BLAST) to find similarities to characterized proteins or by using HMMer to find similarities to enzyme models (usually from TIGRFams). For alignments to characterized proteins (from ublast), scores of 44 bits correspond to an expectation value (E) of about 0.001.
Definition of step leuA
- Curated proteins or TIGRFams with EC 2.3.3.13 (search)
- UniProt sequence L0G5E1_ECHVK: SubName: Full=Isopropylmalate/homocitrate/citramalate synthase {ECO:0000313|EMBL:AGA80045.1};
- UniProt sequence A0A1X9Z750_9SPHI: SubName: Full=2-isopropylmalate synthase {ECO:0000313|EMBL:ARS41048.1};
- Ignore hits to items matching isopropylmalate synthase when looking for 'other' hits
- Ignore hits to P85362 when looking for 'other' hits (2-isopropylmalate synthase; Alpha-IPM synthase; Alpha-isopropylmalate synthase; EC 2.3.3.13)
- Ignore hits to S3D9F8 when looking for 'other' hits (Isopropyl malate synthase gloH; L-homotyrosine biosynthesis sub-cluster protein gloH; Pneumocandin biosynthesis cluster protein H; EC 2.3.3.13)
- Ignore hits to K0E4E5 when looking for 'other' hits (Isopropyl malate synthase htyA; L-homotyrosine biosynthetic cluster protein A; EC 2.3.3.13. 2-(4-hydroxybenzyl)-malate synthase)
- Comment: Ignore CharProtDB entries with no EC number. Add Echvi_3833 (L0G5E1_ECHVK) and CA265_RS15855 (A0A1X9Z750_9SPHI), which are supported by fitness data. P85362 is ignored because it is just 9 amino acids. S3D9F8 and K0E4E5 are involved in secondary metabolite synthesis and it is not clear if they actually have this activity, so they are ignored.
Or cluster all characterized leuA proteins
This GapMind analysis is from Jul 25 2024. The underlying query database was built on Jul 25 2024.
Links
Downloads
Related tools
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