Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) · seed P9WGR1 · 269 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P9WGR1 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.40.50.720 SCOP 8057189 SCOP 8063136 SCOP 8063142 SCOP 8063132 SCOP 8058479 SCOP 8054262 SCOP 8063146 SCOP 8094683 SCOP 8063160 SCOP 8101219 SCOP 8101367 SCOP 8063164 SCOP 8063150 SCOP 8104313 SCOP 8096252 SCOP 8063158 SCOP 8063162 SCOP 8100452 SCOP 8058483 SCOP 8083274 RCSB 5COQ PDBe
CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.
Every figure here is counted over the whole family rather than quoted from one entry.
5COQ, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.
How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.
85 distinct constructs across 290 entries. 174 polymer entities differ from the UniProt canonical sequence in some way, 94 carry a recognised expression tag and 0 carry a fusion partner.
"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.
| Entities | Length | Best (Å) | Best entry | What was made |
|---|---|---|---|---|
| 42 | 269 | 1.40 | 4TRO | matches the canonical sequence |
| 30 | 272 | 1.51 | 28IQ | matches the canonical sequence |
| 23 | 282 | 1.80 | 4D44 | His6 |
| 13 | 289 | 1.60 | 4OHU | His6; Thrombin site |
| 11 | 269 | 1.71 | 5OIP | T2A |
| 11 | 276 | 1.59 | 5I7S | His6 |
| 7 | 262 | 2.00 | 1C14 | matches the canonical sequence |
| 7 | 329 | 1.96 | 3LT0 | residues 96-424 |
| 6 | 270 | 1.72 | 6SQD | matches the canonical sequence |
| 5 | 261 | 1.50 | 2WYU | matches the canonical sequence |
| 5 | 261 | 1.90 | 1QG6 | residues 2-262 |
| 5 | 280 | 1.85 | 4J3F | His6; Thrombin site |
| 5 | 336 | 2.40 | 1VRW | residues 97-432 |
| 4 | 229 | 2.35 | 1NHW | residues 97-325 |
| 4 | 268 | 2.20 | 1ENY | residues 2-269; T2A |
| 4 | 315 | 2.00 | 4O1M | residues 103-417 |
| 4 | 338 | 2.10 | 2OOS | residues 88-425; N88M, K89V, I90H +7 more |
| 3 | 258 | 1.85 | 5YCV | matches the canonical sequence |
| 3 | 261 | 1.90 | 4M89 | matches the canonical sequence |
| 3 | 269 | 1.90 | 4DTI | S94A |
| 3 | 270 | 1.80 | 4CV2 | His6 |
| 3 | 277 | 1.45 | 7U0M | His6 |
| 3 | 287 | 2.12 | 7F44 | His6; TEV site; G222Q |
| 3 | 289 | 2.00 | 5CPB | His6; Thrombin site; I215A |
| 3 | 305 | 1.97 | 5CFZ | His6+S-tag; Enterokinase site |
Showing the 25 most-used of 85.
Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| tetrameric | 4 | 261 | 90.0% |
| dimeric | 2 | 18 | 6.2% |
| monomeric | 1 | 8 | 2.8% |
| octameric | 8 | 2 | 0.7% |
| hexameric | 6 | 1 | 0.3% |
261 entries have the depositor's assembly corroborated by PISA, 22 carry the depositor's word alone and 7 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 19 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1BVR, 1ENY, 1ENZ, 1NHG, 1NHW, 1NNU, 1VRW, 2FHS, 2FOI, 3GNS, 3GNT, 4DRE, 4J1N, 4J3F, 4J4T, 5VRL, 5VRM, 5VRN, 5W07.
Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.
| Domain | Source | Span (seed) | Chains |
|---|---|---|---|
| NAD(P)-binding Rossmann-like Domain | CATH 3.40.50.720 | 5–269 | 240 |
| SDR-like | SCOP2B 8057189 | 4–260 | 25 |
| SDR-like | SCOP2B 8063136 | 4–260 | 10 |
| SDR-like | SCOP2B 8063142 | 4–262 | 2 |
| SDR-like | SCOP2B 8063132 | 4–260 | 2 |
| SDR-like | SCOP2B 8058479 | 5–260 | 5 |
| SDR-like | SCOP2B 8054262 | 7–262 | 125 |
| SDR-like | SCOP2B 8063146 | 7–261 | 7 |
| SDR-like | SCOP2B 8094683 | 9–268 | 4 |
| SDR-like | SCOP2B 8063160 | 10–263 | 6 |
| SDR-like | SCOP2B 8101219 | 10–269 | 2 |
| SDR-like | SCOP2B 8101367 | 11–269 | 3 |
NAD193 entries
TCL30 entries
NAP24 entries
GLU17 entries
NAI13 entries
NDP8 entries
ZID7 entries
TCU5 entries
0WE4 entries
ETX4 entries
PYW3 entries
1S53 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| NAD | cofactor | Nicotinamide-Adenine-Dinucleotide | 193 | 1.20 |
| TCL | ligand | Triclosan | 30 | 1.74 |
| NAP | cofactor | Nadp Nicotinamide-Adenine-Dinucleotide Phosphate | 24 | 1.49 |
| NA | ion | Sodium Ion | 20 | 1.20 |
| GLU | ligand | Glutamic Acid | 17 | 1.80 |
| SO4 | ion | Sulfate Ion | 14 | 1.75 |
| GOL | cryoprotectant | Glycerol | 14 | 1.50 |
| NAI | cofactor | 1,4-Dihydronicotinamide Adenine Dinucleotide | 13 | 1.80 |
| CL | ion | Chloride Ion | 12 | 1.86 |
| ACT | cryoprotectant | Acetate Ion | 11 | 1.60 |
| EDO | cryoprotectant | 1,2-Ethanediol | 11 | 1.60 |
| NDP | cofactor | Nadph Dihydro-Nicotinamide-Adenine-Dinucleotide Phosphate | 8 | 1.85 |
| ZID | ligand | Isonicotinic-Acetyl-Nicotinamide-Adenine Dinucleotide | 7 | 1.40 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 7 | 1.40 |
| MPD | cryoprotectant | (4s)-2-Methyl-2,4-Pentanediol | 6 | 1.80 |
| MG | ion | Magnesium Ion | 6 | 1.64 |
| TCU | ligand | 5-Hexyl-2-(2-Methylphenoxy)phenol | 5 | 1.81 |
| EPE | buffer | 4-(2-Hydroxyethyl)-1-Piperazine Ethanesulfonic Acid | 5 | 1.40 |
| 0WE | ligand | N-Methyl-N-[(3-Methyl-1-Benzofuran-2-Yl)methyl]-3-(7-Oxo-5,6,7,8 | 4 | 1.80 |
| ETX | ligand | 2-Ethoxyethanol | 4 | 1.87 |
Parsed from the free text 267 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 274
entries that recorded anything at all.
Median pH 6.8
(range 4.2 to 10.5).
289 entries carry a wwPDB validation report: 155 clean, 75 worth a check and 59 with something to explain. Median clashscore 4.64, median RSRZ outliers 2.44%, median R-free minus R-work 0.038. 273 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Mycobacterium tuberculosis | 68 | 1.40 | 59 | 100% |
| Mycobacterium tuberculosis H37Rv | 52 | 1.54 | 52 | 100% |
| Plasmodium falciparum | 23 | 1.96 | 23 | 30% |
| Staphylococcus aureus | 15 | 1.90 | 11 | 97% |
| Staphylococcus aureus subsp. aureus N315 | 13 | 1.80 | 13 | 97% |
| Escherichia coli | 12 | 1.75 | 12 | 97% |
| Burkholderia pseudomallei | 10 | 1.59 | 9 | 97% |
| Mycobacterium tuberculosis CDC1551 | 8 | 1.73 | 8 | 100% |
| Escherichia coli K-12 | 8 | 1.90 | 7 | 97% |
| Bacillus cereus ATCC 14579 | 6 | 1.70 | 3 | 97% |
| Helicobacter pylori | 5 | 1.80 | 4 | 98% |
| Streptomyces xanthophaeus | 4 | 1.49 | 4 | 48% |
269 residues, numbered every ten. Every identity figure in this document is measured against this sequence.
active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions
Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 2026 | Rational Design of Diaryl Ether-Based Dual Inhibitors Targeting Successive Essential Enzymes HadAB and InhA in Mycobacterium tuberculosis . J.Med.Chem. doi:10.1021/acs.jmedchem.6c01302 |
| 2026 | Optimizing the Antibiotic Potency and Metabolic Stability of Pyridomycin Using a Semisynthetic Approach. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02409 |
| 2025 | The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant Neisseria gonorrhoeae infection in vivo. Nat Commun doi:10.1038/s41467-025-63508-w |
| 2024 | Structural and Biochemical Studies on Klebsiella Pneumoniae Enoyl-ACP Reductase (FabI) Suggest Flexible Substrate Binding Site. Protein J. doi:10.1007/s10930-023-10176-8 |
| 2023 | Discovery of new diaryl ether inhibitors against Mycobacterium tuberculosis targeting the minor portal of InhA. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2023.115646 |
| 2023 | In Vitro and In Vivo Efficacy of NITD-916 against Mycobacterium fortuitum. Antimicrob.Agents Chemother. doi:10.1128/aac.01607-22 |
| 2023 | The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202313109 |
| 2023 | Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors. Bioorg.Chem. doi:10.1016/j.bioorg.2023.107032 |
| 2022 | Efficacy and Mode of Action of a Direct Inhibitor of Mycobacterium abscessus InhA. Acs Infect Dis. doi:10.1021/acsinfecdis.2c00314 |
| 2022 | An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections Acs Cent.Sci. doi:10.1021/acscentsci.2c00969 |
| 2022 | Biochemical and structural basis for Moraxella catarrhalis enoyl-acyl carrier protein reductase (FabI) inhibition by triclosan and estradiol. Biochimie doi:10.1016/j.biochi.2022.02.008 |
| 2022 | Inhibition of Mycobacterium tuberculosis InhA by 3-nitropropanoic acid. Proteins doi:10.1002/prot.26268 |
| 2021 | A Long Residence Time Enoyl-Reductase Inhibitor Explores an Extended Binding Region with Isoenzyme-Dependent Tautomer Adaptation and Differential Substrate-Binding Loop Closure. Acs Infect Dis. doi:10.1021/acsinfecdis.0c00437 |
| 2020 | Fragment-Based Design ofMycobacterium tuberculosisInhA Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.0c00007 |
| 2020 | The genome of a Bacteroidetes inhabitant of the human gut encodes a structurally distinct enoyl-acyl carrier protein reductase (FabI). J.Biol.Chem. doi:10.1074/jbc.RA120.013336 |
| 2020 | Discovery of New and Potent InhA Inhibitors as Antituberculosis Agents: Structure-Based Virtual Screening Validated by Biological Assays and X-ray Crystallography. J.Chem.Inf.Model. doi:10.1021/acs.jcim.9b00918 |
| 2020 | Ternary complex formation of AFN-1252 with Acinetobacter baumannii FabI and NADH: Crystallographic and biochemical studies. Chem.Biol.Drug Des. doi:10.1111/cbdd.13686 |
| 2020 | The Kalimantacin Polyketide Antibiotics Inhibit Fatty Acid Biosynthesis in Staphylococcus aureus by Targeting the Enoyl-Acyl Carrier Protein Binding Site of FabI. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.201915407 |
| 2018 | Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA. ChemMedChem doi:10.1002/cmdc.201700774 |
| 2018 | InhA, the enoyl-thioester reductase fromMycobacterium tuberculosisforms a covalent adduct during catalysis. J. Biol. Chem. doi:10.1074/jbc.RA118.005405 |
| 2018 | Discovery of a cofactor-independent inhibitor ofMycobacterium tuberculosisInhA. Life Sci Alliance doi:10.26508/lsa.201800025 |
| 2017 | Rationalizing the Binding Kinetics for the Inhibition of the Burkholderia pseudomallei FabI1 Enoyl-ACP Reductase. Biochemistry doi:10.1021/acs.biochem.6b01048 |
| 2017 | Structural insights into the dimer-tetramer transition of FabI from Bacillus anthracis Biochem. Biophys. Res. Commun. doi:10.1016/j.bbrc.2017.09.084 |
| 2017 | Evaluating the Contribution of Transition-State Destabilization to Changes in the Residence Time of Triazole-Based InhA Inhibitors. J. Am. Chem. Soc. doi:10.1021/jacs.6b11148 |
| 2016 | Discovery of Cofactor-Specific, Bactericidal Mycobacterium Tuberculosis Inha Inhibitors Using DNA-Encoded Library Technology Proc.Natl.Acad.Sci.USA doi:10.1073/PNAS.1610978113 |
| 2016 | N-Benzyl-4-((heteroaryl)methyl)benzamides: A New Class of Direct NADH-Dependent 2-trans Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity. Chemmedchem doi:10.1002/cmdc.201600020 |
| 2016 | Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. Ebiomedicine doi:10.1016/j.ebiom.2016.05.006 |
| 2015 | Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. J.Struct.Biol. doi:10.1016/j.jsb.2015.04.008 |
| 2015 | Crystal Structures of Pseudomonas aeruginosa Enoyl-ACP Reductase (FabI) in the Presence and Absence of NAD+ and Triclosan Bull.Korean Chem.Soc. doi:10.1002/bkcs.10084 |
| 2015 | An Ordered Water Channel in Staphylococcus Aureus Fabi: Unraveling the Mechanism of Substrate Recognition and Reduction. Biochemistry doi:10.1021/BI5014358 |
| 2015 | Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI). Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2015.01.048 |
| 2015 | Crystallographic insights into the structure-activity relationships of diazaborine enoyl-ACP reductase inhibitors. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X15022098 |
| 2015 | Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA. Biochemistry doi:10.1021/acs.biochem.5b00284 |
| 2015 | Direct inhibitors of InhA are active against Mycobacterium tuberculosis Sci Transl Med doi:10.1126/scitranslmed.3010597 |
| 2014 | A Structural and Energetic Model for the Slow-Onset Inhibition of the Mycobacterium tuberculosis Enoyl-ACP Reductase InhA. Acs Chem.Biol. doi:10.1021/cb400896g |
| 2014 | Rational Design of Broad Spectrum Antibacterial Activity Based on a Clinically Relevant Enoyl-Acyl Carrier Protein (Acp) Reductase Inhibitor. J.Biol.Chem. doi:10.1074/JBC.M113.532804 |
| 2014 | Time-Dependent Diaryl Ether Inhibitors of InhA: Structure-Activity Relationship Studies of Enzyme Inhibition, Antibacterial Activity, and in vivo Efficacy. Chemmedchem doi:10.1002/cmdc.201300429 |
| 2014 | Pyridomycin Bridges the Nadh and Substrate Binding Pockets of the Enoyl Reductase Inha Nat.Chem.Biol. doi:10.1038/NCHEMBIO.1405 |
| 2014 | The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2013.12.066 |
| 2014 | Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium Tuberculosis Inha. J.Med.Chem. doi:10.1021/JM401326J |