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Structures of Escherichia coli histidinol-phosphate aminotransferase and its complexes with histidinol-phosphate and N-(5'-phosphopyridoxyl)-L-glutamate: double substrate recognition of the enzyme.

Haruyama K, Nakai T, Miyahara I, Hirotsu K, Mizuguchi H, Hayashi H, Kagamiyama H
Biochemistry 40 4633-44 (2001)
Related entries: 1gew, 1gey

Cited: 23 times
EuropePMC logo PMID: 11294630

Abstract

Histidinol-phosphate aminotransferase (HspAT) is a key enzyme on the histidine biosynthetic pathway. HspAT catalyzes the transfer of the amino group of L-histidinol phosphate (Hsp) to 2-oxoglutarate to form imidazole acetol phosphate (IAP) and glutamate. Thus, HspAT recognizes two kinds of substrates, Hsp and glutamate (double substrate recognition). The crystal structures of native HspAT and its complexes with Hsp and N-(5'-phosphopyridoxyl)-L-glutamate have been solved and refined to R-factors of 19.7, 19.1, and 17.8% at 2.0, 2.2, and 2.3 A resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of the subunit is folded into one arm, one small domain, and one large domain. Aspartate aminotransferases (AspATs) from many species were classified into aminotransferase subgroups Ia and Ib. The primary sequence of HspAT is less than 18% identical to those of Escherichia coli AspAT of subgroup Ia and Thermus thermophilus HB8 AspAT of subgroup Ib. The X-ray analysis of HspAT showed that the overall structure is significantly similar to that of AspAT of subgroup Ib rather than subgroup Ia, and the N-terminal region moves close to the active site like that of subgroup Ib AspAT upon binding of Hsp. The folding of the main-chain atoms in the active site is conserved between HspAT and the AspATs, and more than 40% of the active-site residues is also conserved. The eHspAT recognizes both Hsp and glutamate by utilizing essentially the same active-site folding as that of AspAT, conserving the essential residues for transamination reaction, and replacing and relocating some of the active-site residues. The binding sites for the phosphate and the alpha-carboxylate groups of the substrates are roughly located at the same position and those for the imidazole and gamma-carboxylate groups at the different positions. The mechanism for the double substrate recognition observed in eHspAT is in contrast to that in aromatic amino acid aminotransferase, where the recognition site for the side chain of the acidic amino acid is formed at the same position as that for the side chain of aromatic amino acids by large-scale rearrangements of the hydrogen bond networks.

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  1. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Eliot AC, Kirsch JF. Annu Rev Biochem 73 383-415 (2004)
  2. Dual substrate recognition of aminotransferases. Hirotsu K, Goto M, Okamoto A, Miyahara I. Chem Rec 5 160-172 (2005)
  3. Evolutionary origin and functional diversification of aminotransferases. Koper K, Han SW, Pastor DC, Yoshikuni Y, Maeda HA. J Biol Chem 298 102122 (2022)
  4. Contribution of structural genomics to understanding the biology of Escherichia coli. Matte A, Sivaraman J, Ekiel I, Gehring K, Jia Z, Cygler M. J Bacteriol 185 3994-4002 (2003)
  5. Molecular modelling studies on the interactions of human DNA topoisomerase IB with pyridoxal-compounds. Christmann-Franck S, Fermandjian S, Mirambeau G, Der Garabedian PA. Biochimie 89 468-473 (2007)

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  1. pH-dependent catabolic protein expression during anaerobic growth of Escherichia coli K-12. Yohannes E, Barnhart DM, Slonczewski JL. J Bacteriol 186 192-199 (2004)
  2. Biosynthesis of Histidine. Winkler ME, Ramos-Montañez S. EcoSal Plus 3 (2009)
  3. Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase. Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M. Proc Natl Acad Sci U S A 99 1859-1864 (2002)
  4. Stereospecific biosynthesis of β-methyltryptophan from (L)-tryptophan features a stereochemical switch. Zou Y, Fang Q, Yin H, Liang Z, Kong D, Bai L, Deng Z, Lin S. Angew Chem Int Ed Engl 52 12951-12955 (2013)
  5. Identification of novel bacterial histidine biosynthesis inhibitors using docking, ensemble rescoring, and whole-cell assays. Henriksen ST, Liu J, Estiu G, Oltvai ZN, Wiest O. Bioorg Med Chem 18 5148-5156 (2010)
  6. Characterization of the PLP-dependent aminotransferase NikK from Streptomyces tendae and its putative role in nikkomycin biosynthesis. Binter A, Oberdorfer G, Hofzumahaus S, Nerstheimer S, Altenbacher G, Gruber K, Macheroux P. FEBS J 278 4122-4135 (2011)
  7. Direct evidence for a glutamate switch necessary for substrate recognition: crystal structures of lysine epsilon-aminotransferase (Rv3290c) from Mycobacterium tuberculosis H37Rv. Mani Tripathi S, Ramachandran R. J Mol Biol 362 877-886 (2006)
  8. Pyridoxal 5'-phosphate inactivates DNA topoisomerase IB by modifying the lysine general acid. Vermeersch JJ, Christmann-Franck S, Karabashyan LV, Fermandjian S, Mirambeau G, Der Garabedian PA. Nucleic Acids Res 32 5649-5657 (2004)
  9. Mechanism of substrate recognition and PLP-induced conformational changes in LL-diaminopimelate aminotransferase from Arabidopsis thaliana. Watanabe N, Clay MD, van Belkum MJ, Cherney MM, Vederas JC, James MN. J Mol Biol 384 1314-1329 (2008)
  10. Chemogenomics of pyridoxal 5'-phosphate dependent enzymes. Singh R, Spyrakis F, Cozzini P, Paiardini A, Pascarella S, Mozzarelli A. J Enzyme Inhib Med Chem 28 183-194 (2013)
  11. Structural analysis and mutant growth properties reveal distinctive enzymatic and cellular roles for the three major L-alanine transaminases of Escherichia coli. Peña-Soler E, Fernandez FJ, López-Estepa M, Garces F, Richardson AJ, Quintana JF, Rudd KE, Coll M, Vega MC. PLoS One 9 e102139 (2014)
  12. Enhanced production of recombinant Escherichia coli glutamate decarboxylase through optimization of induction strategy and addition of pyridoxine. Su L, Huang Y, Wu J. Bioresour Technol 198 63-69 (2015)
  13. Functional Characterization of Two PLP-Dependent Enzymes Involved in Capsular Polysaccharide Biosynthesis from Campylobacter jejuni. Riegert AS, Narindoshvili T, Coricello A, Richards NGJ, Raushel FM. Biochemistry 60 2836-2843 (2021)
  14. Dual roles of a conserved pair, Arg23 and Ser20, in recognition of multiple substrates in alpha-aminoadipate aminotransferase from Thermus thermophilus. Ouchi T, Tomita T, Miyagawa T, Kuzuyama T, Nishiyama M. Biochem Biophys Res Commun 388 21-27 (2009)
  15. Crystal structures of Mycobacterium tuberculosis HspAT and ArAT reveal structural basis of their distinct substrate specificities. Nasir N, Anant A, Vyas R, Biswal BK. Sci Rep 6 18880 (2016)
  16. Characterization of the Aminotransferase ThdN from Thienodolin Biosynthesis in Streptomyces albogriseolus. Milbredt D, Patallo EP, van Pée KH. Chembiochem 17 1859-1864 (2016)
  17. The first steps. The attack on the carbonyl carbon of pyridoxal cofactor in pyridoxal-dependent enzymes. Sonnet PE, Mascavage LM, Dalton DR. Bioorg Med Chem Lett 18 744-748 (2008)


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