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Gene Review

AASDHPPT  -  aminoadipate-semialdehyde dehydrogenase...

Homo sapiens

Synonyms: 4'-phosphopantetheinyl transferase, AASD-PPT, Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase, CGI-80, HAH-P, ...
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Disease relevance of AASDHPPT

  • Together, these data demonstrate that Lys5, Leu6, Phe9, and Val10 preferentially interact with C(6)PS and allow us to correlate known hemophilia B mutations of factor IX at Lys5 or Phe9 with impaired phosphatidylserine interaction [1].

High impact information on AASDHPPT

  • Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity [2].
  • Myxothiazol, an inhibitor of the electron transport via the bc(1)-complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), which are activated by the 4'-phosphopantetheinyl transferase MtaA [3].
  • This suggests that long-range coulombic interactions such as those originating from Lys5 and Lys7 of CspB can be important for organizing and stabilizing native-like structure early in protein folding [4].
  • Interestingly, replacing the terminal Lys residues of L24 by 2,3-diaminopropionic acid residues actually attenuates the hydrophobic mismatch effects of the peptide on the thermotropic phase behavior of the host PC bilayer, in contrast to the predictions of the snorkel hypothesis [5].
  • Each lysine residue that was added to Lys2 decreased by one order of magnitude the concentration of peptide required to reverse the charge on the vesicle; equivalently it increased by one order of magnitude the binding affinity of the peptides for the PS vesicles [6].

Biological context of AASDHPPT

  • The mutagenesis technology was applied to the gene region coding for positions Lys2 to Thr13 (N half) and Ala14 to Leu25 (C half) of the signal peptide [7].
  • A 5.2-kb NotI DNA fragment isolated from a genomic library of Acremonium chrysogenum by hybridization with a probe internal to the Penicillium chrysogenum lys2 gene, was able to complement an alpha-aminoadipate reductase-deficient mutant of P. chrysogenum (lysine auxotroph L-G-) [8].
  • The lys2 gene was mapped to chromosome I (2.2 Mb, the smallest chromosome) of A. chrysogenum C10 (the chromosome that contains the "late" cephalosporin cluster) and is transcribed as a monocistronic 4.5-kb mRNA although at relatively low levels compared with the beta-actin gene [8].

Anatomical context of AASDHPPT

  • Histone H2B could be studied in detail only from butyrate-treated HeLa cells and a much lower level of site specificity was found: sites 12 and 15 were preferred to the more N- and C-terminal sites at Lys5 and Lys20 [9].
  • Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood [10].

Associations of AASDHPPT with chemical compounds

  • Backbone amide protons of Phe4 and Ala13 and the backbone carbonyl oxygen of Lys2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively [11].
  • RESULTS: The NK-2 receptor agonists neurokinin A (NKA), neuropeptide gamma and [Lys5, MeLeu9, Nle10]-NKA(4-10) contracted the isolated child detrusor, with pD2 values of 7.7, 7.2 and 7 [12].
  • NK-2-selective antagonists also competed for INKA binding, with SR 48968, GR 94800, MDL 29913 and the selective agonist [Lys5, MeLeu9, Nle10]-NKA(4-10) showing biphasic binding profiles [13].
  • Tachykinins contracted detrusor muscle strips, with potency order at the carbachol EC15 NKA = kassinin > [Lys5, MeLeu9, Nle10]-NKA(4-10) = neuropeptide gamma = neuropeptide K = NKB > > MDL 28564, with [Sar9, Met(O2)11]-SP ineffective [13].
  • Characterization of the lys2 gene of Acremonium chrysogenum encoding a functional alpha-aminoadipate activating and reducing enzyme [8].

Analytical, diagnostic and therapeutic context of AASDHPPT

  • High-sensitivity differential scanning calorimetry and Fourier transform infrared spectroscopy were used to study the interaction of a cationic alpha-helical transmembrane peptide, acetyl-Lys2-Leu24-Lys2-amide (L24), and members of the homologous series of zwitterionic n-saturated diacyl phosphatidylethanolamines (PEs) [14].
  • The interactions between basic oligopeptides (Lys2, Lys3, Arg2 and Arg3) and single stranded polynucleotides (poly(A), poly(C), poly(I) and poly(U) were investigated at low ion concentration by UV spectroscopy, circular dichroism and field jump relaxation [15].


  1. Lysine 5 and phenylalanine 9 of the factor IX omega-loop interact with phosphatidylserine in a membrane-mimetic environment. Grant, M.A., Baikeev, R.F., Gilbert, G.E., Rigby, A.C. Biochemistry (2004) [Pubmed]
  2. Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity. Joshi, A.K., Zhang, L., Rangan, V.S., Smith, S. J. Biol. Chem. (2003) [Pubmed]
  3. New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1. Silakowski, B., Schairer, H.U., Ehret, H., Kunze, B., Weinig, S., Nordsiek, G., Brandt, P., Blöcker, H., Höfle, G., Beyer, S., Müller, R. J. Biol. Chem. (1999) [Pubmed]
  4. Key role of coulombic interactions for the folding transition state of the cold shock protein. Garcia-Mira, M.M., Schmid, F.X. J. Mol. Biol. (2006) [Pubmed]
  5. Effect of variations in the structure of a polyleucine-based alpha-helical transmembrane peptide on its interaction with phosphatidylcholine bilayers. Liu, F., Lewis, R.N., Hodges, R.S., McElhaney, R.N. Biochemistry (2002) [Pubmed]
  6. Binding of peptides with basic residues to membranes containing acidic phospholipids. Kim, J., Mosior, M., Chung, L.A., Wu, H., McLaughlin, S. Biophys. J. (1991) [Pubmed]
  7. Improvement of an unusual twin-arginine transporter leader Peptide by a codon-based randomization approach. Monroy-Lagos, O., Soberon, X., Gaytan, P., Osuna, J. Appl. Environ. Microbiol. (2006) [Pubmed]
  8. Characterization of the lys2 gene of Acremonium chrysogenum encoding a functional alpha-aminoadipate activating and reducing enzyme. Hijarrubia, M.J., Aparicio, J.F., Casqueiro, J., Martín, J.F. Mol. Gen. Genet. (2001) [Pubmed]
  9. Patterns of histone acetylation. Thorne, A.W., Kmiciek, D., Mitchelson, K., Sautiere, P., Crane-Robinson, C. Eur. J. Biochem. (1990) [Pubmed]
  10. Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin. Oberg, G., Simonsson, B., Smedmyr, B., Tötterman, T.H., Venge, P. Eur. J. Haematol. (1987) [Pubmed]
  11. Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC. South, T.L., Summers, M.F. Protein Sci. (1993) [Pubmed]
  12. Tachykinin NK-2 receptors in child urinary bladder. Zeng, X.P., Burcher, E. J. Urol. (1996) [Pubmed]
  13. Radioligand binding, autoradiographic and functional studies demonstrate tachykinin NK-2 receptors in dog urinary bladder. Mussap, C.J., Stamatakos, C., Burcher, E. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  14. Effect of variations in the structure of a polyleucine-based alpha-helical transmembrane peptide on its interaction with phosphatidylethanolamine Bilayers. Liu, F., Lewis, R.N., Hodges, R.S., McElhaney, R.N. Biophys. J. (2004) [Pubmed]
  15. The binding of Arg- and Lys-peptides to single stranded polyribonucleotides and its effect on the polymer conformation. Porschke, D. Biophys. Chem. (1979) [Pubmed]
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