1p45

X-ray diffraction
2.6Å resolution

Targeting tuberculosis and malaria through inhibition of enoyl reductase: compound activity and structural data

Released:

Function and Biology Details

Reactions catalysed:
A beta-lactam + H(2)O = a substituted beta-amino acid
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
D-ribose 5-phosphate = D-ribulose 5-phosphate
S-adenosyl 3-(methylthio)propylamine + putrescine = 5'-S-methyl-5'-thioadenosine + spermidine
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
L-fuculose 1-phosphate = glycerone phosphate + (S)-lactaldehyde
Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs).
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
Isochorismate = salicylate + pyruvate
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
1-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = ATP + 5-phospho-alpha-D-ribose 1-diphosphate
Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+)
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cyteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cyteine
(2Z,6E)-farnesyl diphosphate + 7 isopentenyl diphosphate = 7 diphosphate + (2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E)-decaprenyl diphosphate
(2E,6E)-farnesyl diphosphate + n isopentenyl diphosphate = n diphosphate + ditrans,polycis-polyprenyl diphosphate (n = 10-55)
N(2)-acetyl-L-ornithine + L-glutamate = L-ornithine + N-acetyl-L-glutamate
Selective cleavage of Tyr-|-Gly bond in picornavirus polyprotein.
An acyl-[acyl-carrier protein] + NAD(+) = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH
S-adenosyl-L-methionine + guanosine(2251) in 23S rRNA = S-adenosyl-L-homocysteine + 2'-O-methylguanosine(2251) in 23S rRNA 
S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
NTP + H(2)O = NDP + phosphate
2-phospho-D-glycerate = phosphoenolpyruvate + H(2)O
ATP + L-tyrosine + tRNA(Tyr) = AMP + diphosphate + L-tyrosyl-tRNA(Tyr)
GTP + H(2)O = GDP + phosphate
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose
Sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate
L-lysine + NADPH + O(2) = N(6)-hydroxy-L-lysine + NADP(+) + H(2)O
Hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides
O-phospho-L-homoserine + H(2)O = L-threonine + phosphate
Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
ATP + H(2)O = ADP + phosphate
ATP + thymidine = ADP + thymidine 5'-phosphate
4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
5,10-methylenetetrahydrofolate + dUMP + NADPH = dTMP + tetrahydrofolate + NADP(+)
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
Chorismate = isochorismate
Diphosphate + H(2)O = 2 phosphate
Chorismate = prephenate
Hydroxymethylbilane = uroporphyrinogen III + H(2)O
Hydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose and similar substrates, releasing cellobiose from the reducing ends of the chains.
Biochemical function:
Biological process:
Cellular component:

Structure analysis Details

Assembly composition:
homo tetramer (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Enoyl-[acyl-carrier-protein] reductase [NADH] Chains: A, B
Molecule details ›
Chains: A, B
Length: 269 amino acids
Theoretical weight: 28.55 KDa
Source organism: Mycobacterium tuberculosis
Expression system: Escherichia coli
UniProt:
  • Canonical: P9WGR1 (Residues: 1-269; Coverage: 100%)
Gene names: MTCY277.05, Rv1484, inhA
Sequence domains: Enoyl-(Acyl carrier protein) reductase
Structure domains: NAD(P)-binding Rossmann-like Domain

Ligands and Environments


Cofactor: Ligand NAD 2 x NAD
1 bound ligand:
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 14-BM-C
Spacegroup: I212121
Unit cell:
a: 94.822Å b: 104.12Å c: 189.746Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.228 0.225 0.29
Expression system: Escherichia coli