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Homoserine dehydrogenase

January 01, 1970

In enzymology, a homoserine dehydrogenase (EC 1.1.1.3) is an enzyme that catalyzes the chemical reaction

Homoserine dehydrogenase
Homoserine dehydrogenase complex with NAD+ analogue and L-homoserine.
Identifiers
SymbolHomoserine_dh
PfamPF00742
InterProIPR001342
PROSITEPDOC00800
SCOP21ebu / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Homoserine dehydrogenase
Homoserine dehydrogenase homotetramer, Thiobacillus denitrificans
Identifiers
EC no.1.1.1.3
CAS no.9028-13-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
L-homoserine + NAD(P)+ L-aspartate 4-semialdehyde + NAD(P)H + H+

The 2 substrates of this enzyme are L-homoserine and NAD+ (or NADP+), whereas its 3 products are L-aspartate 4-semialdehyde, NADH (or NADPH), and H+.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-homoserine:NAD(P)+ oxidoreductase. Other names in common use include HSDH, and HSD.

Homoserine dehydrogenase catalyses the third step in the aspartate pathway; the NAD(P)-dependent reduction of aspartate beta-semialdehyde into homoserine.[1][2] Homoserine is an intermediate in the biosynthesis of threonine, isoleucine, and methionine.[3]

Enzyme structure edit

The enzyme can be found in a monofunctional form, in some bacteria and yeast. Structural analysis of the yeast monofunctional enzyme indicates that the enzyme is a dimer composed of three distinct regions; an N-terminal nucleotide-binding domain, a short central dimerisation region, and a C-terminal catalytic domain.[4] The N-terminal domain forms a modified Rossmann fold, while the catalytic domain forms a novel alpha-beta mixed sheet.

The enzyme can also be found in a bifunctional form consisting of an N-terminal aspartokinase domain and a C-terminal homoserine dehydrogenase domain, as found in bacteria such as Escherichia coli and in plants.[5]

The bifunctional aspartokinase-homoserine dehydrogenase (AK-HSD) enzyme has a regulatory domain that consists of two subdomains with a common loop-alpha helix-loop-beta strand loop-beta strand motif. Each subdomain contains an ACT domain that allows for complex regulation of several different protein functions.[5] The AK-HSD gene codes for aspartate kinase, an intermediate domain (coding for the linker region between the two enzymes in the bifunctional form), and finally the coding sequence for homoserine dehydrogenase.[6][7]

As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1EBF, 1EBU, 1Q7G, and 1TVE.

Enzyme mechanism edit

 
Figure 1. Hypothesized hydride transfer reaction mechanism catalyzed by homoserine dehydrogenase and NAD(P)H.
 
Figure 2. Cartoon representation of the active site of homoserine dehydrogenase (PBD 1EBU).

Homoserine dehydrogenase catalyzes the reaction of aspartate-semialdehyde (ASA) to homoserine. The overall reaction reduces the C4 carboxylic acid functional group of ASA to a primary alcohol and oxidizes the C1 aldehyde to a carboxylic acid. Residues Glu 208 and Lys 117 are thought to be involved in the active catalytic site of the enzyme. Asp 214 and Lys 223 have been shown to be important for hydride transfer in the catalyzed reaction.[4]

Once the C4 carboxylic acid is reduced to an aldehyde and the C1 aldehyde is oxidized to a carboxylic acid, experiments suggest that Asp 219, Glu 208 and a water molecule bind ASA in the active site while Lys 223 donates a proton to the aspartate-semialdehyde C4 oxygen. Homoserine dehydrogenase has an NAD(P)H cofactor, which then donates a hydrogen to the same carbon, effectively reducing the aldehyde to an alcohol.[4] (Refer to figures 1 and 2).

However, the precise mechanism of complete homoserine dehydrogenase catalysis remains unknown.[4]

The homoserine dehydrogenase-catalyzed reaction has been postulated to proceed through a bi-bi kinetic mechanism, where the NAD(P)H cofactor binds the enzyme first and is the last to dissociate from the enzyme once the reaction is complete.[6][8] Additionally, while both NADH and NADPH are adequate cofactors for the reaction, NADH is preferred. The Km of the reaction is four-times smaller with NADH and the Kcat/Km is three-times greater, indicating a more efficient reaction.[9]

Homoserine dehydrogenase also exhibits multi-order kinetics at subsaturating levels of substrate. Additionally, the variable kinetics for homoserine dehydrogenase is an artifact of the faster dissociation of the amino acid substrate from the enzyme complex as compared to cofactor dissociation.[8][10]

Biological function edit

The aspartate metabolic pathway is involved in both storage of asparagine and in synthesis of aspartate-family amino acids.[11] Homoserine dehydrogenase catalyzes an intermediate step in this nitrogen and carbon storage and utilization pathway.[12] (Refer to figure 3).

In photosynthetic organisms, glutamine, glutamate, and aspartate accumulate during the day and are used to synthesize other amino acids. At night, aspartate is converted to asparagine for storage.[12] Additionally, the aspartate kinase-homoserine dehydrogenase gene is primarily expressed in actively growing, young plant tissues, particularly in the apical and lateral meristems.[13]

Mammals lack the enzymes involved in the aspartate metabolic pathway, including homoserine dehydrogenase. As lysine, threonine, methionine, and isoleucine are made in this pathway, they are considered essential amino acids for mammals.[6]

Biological regulation edit

 
Figure 3. Homoserine dehydrogenase is an enzyme involved in the biosynthetic pathway of several key amino acids. It is negatively regulated by threonine, and the pathway is subject to additional regulation.

Homoserine dehydrogenase and aspartate kinase are both subject to significant regulation (refer to figure 3). HSD is inhibited by downstream products of the aspartate metabolic pathway, mainly threonine. Threonine acts as a competitive inhibitor for both HSD and aspartate kinase.[14] In AK-HSD expressing organisms, one of the threonine binding sites is found in the linker region between AK and HSD, suggesting potential allosteric inhibition of both enzymes.[6]

However, some threonine-resistant HSD forms exist that require concentrations of threonine much greater than physiologically present for inhibition. These threonine-insensitive forms of HSD are used in genetically engineered plants to increase both threonine and methionine production for higher nutritional value.[6]

Homoserine dehydrogenase is also subject to transcriptional regulation. Its promoter sequence contains a cis-regulatory element TGACTC sequence, which is known to be involved in other amino acid biosynthetic pathways. The Opaque2 regulatory element has also been implicated in homoserine dehydrogenase regulation, but its effects are still not well defined.[7]

In plants, there is also environmental regulation of AK-HSD gene expression. Light exposure has been demonstrated to increase expression of the AK-HSD gene, presumably related to photosynthesis.[12][13]

Disease relevance edit

In humans, there has been a significant increase in disease from pathogenic fungi, so developing anti-fungal drugs is an important biochemical task.[15] As homoserine dehydrogenase is found mainly in plants, bacteria, and yeast, but not mammals, it is a strong target for antifungal drug development.[16] Recently, 5-hydroxy-4-oxonorvaline (HON) was discovered to target and inhibit HSD activity irreversibly. HON is structurally similar to aspartate semialdehyde, so it is postulated that it serves as a competitive inhibitor for HSD. Likewise, (S) 2-amino-4-oxo-5-hydroxypentanoic acid (RI-331), another amino acid analog, has also been shown to inhibit HSD.[16] Both of these compounds are effective against Cryptococcus neoformans and Cladosporium fulvum, among others.[17]

In addition to amino acid analogs, several phenolic compounds have been shown to inhibit HSD activity. Like HON and RI-331, these molecules are competitive inhibitors that bind to the enzyme active site. Specifically, the phenolic hydroxyl group interacts with the amino acid binding site.[15][18]

References edit

  1. ^ Thomas D, Barbey R, Surdin-Kerjan Y (June 1993). "Evolutionary relationships between yeast and bacterial homoserine dehydrogenases". FEBS Lett. 323 (3): 289–93. doi:10.1016/0014-5793(93)81359-8. PMID 8500624. S2CID 23964791.
  2. ^ Cami B, Clepet C, Patte JC (1993). "Evolutionary comparisons of three enzymes of the threonine biosynthetic pathway among several microbial species". Biochimie. 75 (6): 487–95. doi:10.1016/0300-9084(93)90115-9. PMID 8395899.
  3. ^ Ferreira RR, Meinhardt LW, Azevedo RA (2006). "Lysine and threonine biosynthesis in sorghum seeds: characterisation of aspartate kinase and homoserine dehydrogenase isoenzymes". Ann. Appl. Biol. 149 (1): 77–86. doi:10.1111/j.1744-7348.2006.00074.x.
  4. ^ a b c d DeLaBarre B, Thompson PR, Wright GD, Berghuis AM (March 2000). "Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases". Nat. Struct. Biol. 7 (3): 238–44. doi:10.1038/73359. PMID 10700284. S2CID 26638309.
  5. ^ a b Paris S, Viemon C, Curien G, Dumas R (February 2003). "Mechanism of Control of Arabidopsis thaliana Aspartate Kinase-Homoserine Dehydrogenase by Threonine". J. Biol. Chem. 278 (7): 5361–5366. doi:10.1074/jbc.M207379200. PMID 12435751.
  6. ^ a b c d e Schroeder AC, Zhu C, Yanamadala SR, Cahoon RE, Arkus KAJ, Wachsstock L, Bleeke J, Krishnan HB, Jez JM (January 2010). "Threonine-insensitive Homoserine Dehydrogenase from Soybean: Genomic Organization, Kinetic Mechanism, and in vivo Activity". J. Biol. Chem. 285 (2): 827–834. doi:10.1074/jbc.M109.068882. PMC 2801284. PMID 19897476.
  7. ^ a b Ghislain M, Frankard V, Vandenbossche D, Matthews BF, Jacobs M (March 1994). "Molecular analysis of the aspartate kinase-homoserine dehydrogenase gene from Arabidopsis thaliana". Plant Mol. Biol. 24 (6): 835–851. doi:10.1007/bf00014439. PMID 8204822. S2CID 6183867.
  8. ^ a b Wedler FC, Ley BW, Shames SL, Rembish SJ, Kushmaul DL (March 1992). "Preferred order random kinetic mechanism for homoserine dehydrogenase of Escherichia coli (Thr-sensitive) aspartokinase/homoserine dehydrogenase-I: Equilibrium Isotope Exchange Kinetics". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1119 (3): 247–249. doi:10.1016/0167-4838(92)90209-v. PMID 1547269.
  9. ^ Jacques SL, Nieman C, Bareicha D, Broadhead G, Kinach R, Honek JF, Wright GD (January 2001). "Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1544 (1–2): 28–41. doi:10.1016/S0167-4838(00)00203-X. PMID 11341914.
  10. ^ Wedler FC, Ley BW (March 1993). "Kinetic and Regulatory Mechanisms for Escherichia coli Homoserine Dehydrogenase-I: Equilibrium Isotope Exchange Kinetics". J. Biol. Chem. 268 (1): 4880–4888. doi:10.1016/S0021-9258(18)53478-5. PMID 8444866.
  11. ^ Azevedo RA (2002). "Analysis of the aspartic acid metabolic pathway using mutant genes". Amino Acids. 22 (3): 217–230. doi:10.1007/s007260200010. PMID 12083066. S2CID 23327489.
  12. ^ a b c Zhu-Shimoni JX, Galili G (March 1998). "Expression of an Arabidopsis Aspartate Kinase/Homoserine Dehydrogenase Gene Is Metabolically Regulated by Photosynthesis-Related Signals but Not by Nitrogenous Compounds". Plant Physiol. 116 (3): 1023–1028. doi:10.1104/pp.116.3.1023. PMC 35071. PMID 9501134.
  13. ^ a b Zhu-Shimoni JX, Lev-Yadun S, Matthews B, Calili C (March 1997). "Expression of an Aspartate Kinase Homoserine Dehydrogenase Gene IS Subject to Specific Spatial and Temporal Regulation in Vegetative Tissues, Flowers, and Developing Seeds". Plant Physiol. 113 (3): 695–706. doi:10.1104/pp.113.3.695. PMC 158187. PMID 12223636.
  14. ^ Park SD, Lee JY, Sim SY, Kim Y, Lee HS (July 2007). "Characteristics of methionine production by an engineered Corynebacterium glutamicum strain". Metab. Eng. 9 (4): 327–336. doi:10.1016/j.ymben.2007.05.001. PMID 17604670.
  15. ^ a b Bareich DC, Nazi I, Wright GD (October 2003). "Simultaneous In Vitro Assay of the First Four Enzymes in the Fungal Aspartate Pathway Identifies a New Class of Aspartate Kinase Inhibitor". Chem. Biol. 10 (10): 967–973. doi:10.1016/j.chembiol.2003.09.016. PMID 14583263.
  16. ^ a b Yamaki H, Yamaguchi M, Tsuruo T, Yamaguchi H (May 1992). "Mechanism of action of an antifungal antibiotich, RI-331, (S) 2-amino-4-oxo-5-hydroxypentanoic acid; kinetics of inactivation of homoserine dehydrogenase from Saccharomyces cerevisiae". J. Antibiot. (Tokyo). 45 (5): 750–755. doi:10.7164/antibiotics.45.750. PMID 1352515.
  17. ^ Jacques SL, Mirza IA, Ejim L, Koteva K, Hughes DW, Green K, Kinach R, Honek JF, Lai HK, Berghuis AM, Wright GD (October 2003). "Enzyme-Assisted Suicide: Molecular Basis for the Antifungal Activity of 5-Hydroxy-4-Oxonorvaline by Potent Inhibition of Homoserine Dehydrogenase". Chem. Biol. 10 (10): 989–995. doi:10.1016/j.chembiol.2003.09.015. PMID 14583265.
  18. ^ Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghui AM, Wright GD (July 2004). "New phenolic inhibitors of yeast homoserine dehydrogenase". Bioorg. Med. Chem. 12 (14): 3825–3830. doi:10.1016/j.bmc.2004.05.009. PMID 15210149.

Further reading edit

  • Black S, Wright NG (1955). "Homoserine dehydrogenase". J. Biol. Chem. 213 (1): 51–60. doi:10.1016/S0021-9258(18)71043-0. PMID 14353905.
  • Starnes WL, Munk P, Maul SB, Cunningham GN, Cox DJ, Shive W (1972). "Threonine-sensitive aspartokinase-homoserine dehydrogenase complex, amino acid composition, molecular weight, and subunit composition of the complex". Biochemistry. 11 (5): 677–87. doi:10.1021/bi00755a003. PMID 4551091.
  • Veron M, Falcoz-Kelly F, Cohen GN (1972). "The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain". Eur. J. Biochem. 28 (4): 520–7. doi:10.1111/j.1432-1033.1972.tb01939.x. PMID 4562990.
This article incorporates text from the public domain Pfam and InterPro: IPR001342

January 01, 1970
homoserine, dehydrogenase, enzymology, homoserine, dehydrogenase, enzyme, that, catalyzes, chemical, reaction, complex, with, analogue, homoserine, identifierssymbolhomoserine, dhpfampf00742interproipr001342prositepdoc00800scop21ebu, scope, supfamavailable, pr. In enzymology a homoserine dehydrogenase EC 1 1 1 3 is an enzyme that catalyzes the chemical reactionHomoserine dehydrogenaseHomoserine dehydrogenase complex with NAD analogue and L homoserine IdentifiersSymbolHomoserine dhPfamPF00742InterProIPR001342PROSITEPDOC00800SCOP21ebu SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Homoserine dehydrogenaseHomoserine dehydrogenase homotetramer Thiobacillus denitrificansIdentifiersEC no 1 1 1 3CAS no 9028 13 1DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins L homoserine NAD P displaystyle rightleftharpoons L aspartate 4 semialdehyde NAD P H H The 2 substrates of this enzyme are L homoserine and NAD or NADP whereas its 3 products are L aspartate 4 semialdehyde NADH or NADPH and H This enzyme belongs to the family of oxidoreductases specifically those acting on the CH OH group of donor with NAD or NADP as acceptor The systematic name of this enzyme class is L homoserine NAD P oxidoreductase Other names in common use include HSDH and HSD Homoserine dehydrogenase catalyses the third step in the aspartate pathway the NAD P dependent reduction of aspartate beta semialdehyde into homoserine 1 2 Homoserine is an intermediate in the biosynthesis of threonine isoleucine and methionine 3 Contents 1 Enzyme structure 2 Enzyme mechanism 3 Biological function 4 Biological regulation 5 Disease relevance 6 References 7 Further readingEnzyme structure editThe enzyme can be found in a monofunctional form in some bacteria and yeast Structural analysis of the yeast monofunctional enzyme indicates that the enzyme is a dimer composed of three distinct regions an N terminal nucleotide binding domain a short central dimerisation region and a C terminal catalytic domain 4 The N terminal domain forms a modified Rossmann fold while the catalytic domain forms a novel alpha beta mixed sheet The enzyme can also be found in a bifunctional form consisting of an N terminal aspartokinase domain and a C terminal homoserine dehydrogenase domain as found in bacteria such as Escherichia coli and in plants 5 The bifunctional aspartokinase homoserine dehydrogenase AK HSD enzyme has a regulatory domain that consists of two subdomains with a common loop alpha helix loop beta strand loop beta strand motif Each subdomain contains an ACT domain that allows for complex regulation of several different protein functions 5 The AK HSD gene codes for aspartate kinase an intermediate domain coding for the linker region between the two enzymes in the bifunctional form and finally the coding sequence for homoserine dehydrogenase 6 7 As of late 2007 4 structures have been solved for this class of enzymes with PDB accession codes 1EBF 1EBU 1Q7G and 1TVE Enzyme mechanism edit nbsp Figure 1 Hypothesized hydride transfer reaction mechanism catalyzed by homoserine dehydrogenase and NAD P H nbsp Figure 2 Cartoon representation of the active site of homoserine dehydrogenase PBD 1EBU Homoserine dehydrogenase catalyzes the reaction of aspartate semialdehyde ASA to homoserine The overall reaction reduces the C4 carboxylic acid functional group of ASA to a primary alcohol and oxidizes the C1 aldehyde to a carboxylic acid Residues Glu 208 and Lys 117 are thought to be involved in the active catalytic site of the enzyme Asp 214 and Lys 223 have been shown to be important for hydride transfer in the catalyzed reaction 4 Once the C4 carboxylic acid is reduced to an aldehyde and the C1 aldehyde is oxidized to a carboxylic acid experiments suggest that Asp 219 Glu 208 and a water molecule bind ASA in the active site while Lys 223 donates a proton to the aspartate semialdehyde C4 oxygen Homoserine dehydrogenase has an NAD P H cofactor which then donates a hydrogen to the same carbon effectively reducing the aldehyde to an alcohol 4 Refer to figures 1 and 2 However the precise mechanism of complete homoserine dehydrogenase catalysis remains unknown 4 The homoserine dehydrogenase catalyzed reaction has been postulated to proceed through a bi bi kinetic mechanism where the NAD P H cofactor binds the enzyme first and is the last to dissociate from the enzyme once the reaction is complete 6 8 Additionally while both NADH and NADPH are adequate cofactors for the reaction NADH is preferred The Km of the reaction is four times smaller with NADH and the Kcat Km is three times greater indicating a more efficient reaction 9 Homoserine dehydrogenase also exhibits multi order kinetics at subsaturating levels of substrate Additionally the variable kinetics for homoserine dehydrogenase is an artifact of the faster dissociation of the amino acid substrate from the enzyme complex as compared to cofactor dissociation 8 10 Biological function editThe aspartate metabolic pathway is involved in both storage of asparagine and in synthesis of aspartate family amino acids 11 Homoserine dehydrogenase catalyzes an intermediate step in this nitrogen and carbon storage and utilization pathway 12 Refer to figure 3 In photosynthetic organisms glutamine glutamate and aspartate accumulate during the day and are used to synthesize other amino acids At night aspartate is converted to asparagine for storage 12 Additionally the aspartate kinase homoserine dehydrogenase gene is primarily expressed in actively growing young plant tissues particularly in the apical and lateral meristems 13 Mammals lack the enzymes involved in the aspartate metabolic pathway including homoserine dehydrogenase As lysine threonine methionine and isoleucine are made in this pathway they are considered essential amino acids for mammals 6 Biological regulation edit nbsp Figure 3 Homoserine dehydrogenase is an enzyme involved in the biosynthetic pathway of several key amino acids It is negatively regulated by threonine and the pathway is subject to additional regulation Homoserine dehydrogenase and aspartate kinase are both subject to significant regulation refer to figure 3 HSD is inhibited by downstream products of the aspartate metabolic pathway mainly threonine Threonine acts as a competitive inhibitor for both HSD and aspartate kinase 14 In AK HSD expressing organisms one of the threonine binding sites is found in the linker region between AK and HSD suggesting potential allosteric inhibition of both enzymes 6 However some threonine resistant HSD forms exist that require concentrations of threonine much greater than physiologically present for inhibition These threonine insensitive forms of HSD are used in genetically engineered plants to increase both threonine and methionine production for higher nutritional value 6 Homoserine dehydrogenase is also subject to transcriptional regulation Its promoter sequence contains a cis regulatory element TGACTC sequence which is known to be involved in other amino acid biosynthetic pathways The Opaque2 regulatory element has also been implicated in homoserine dehydrogenase regulation but its effects are still not well defined 7 In plants there is also environmental regulation of AK HSD gene expression Light exposure has been demonstrated to increase expression of the AK HSD gene presumably related to photosynthesis 12 13 Disease relevance editIn humans there has been a significant increase in disease from pathogenic fungi so developing anti fungal drugs is an important biochemical task 15 As homoserine dehydrogenase is found mainly in plants bacteria and yeast but not mammals it is a strong target for antifungal drug development 16 Recently 5 hydroxy 4 oxonorvaline HON was discovered to target and inhibit HSD activity irreversibly HON is structurally similar to aspartate semialdehyde so it is postulated that it serves as a competitive inhibitor for HSD Likewise S 2 amino 4 oxo 5 hydroxypentanoic acid RI 331 another amino acid analog has also been shown to inhibit HSD 16 Both of these compounds are effective against Cryptococcus neoformans and Cladosporium fulvum among others 17 In addition to amino acid analogs several phenolic compounds have been shown to inhibit HSD activity Like HON and RI 331 these molecules are competitive inhibitors that bind to the enzyme active site Specifically the phenolic hydroxyl group interacts with the amino acid binding site 15 18 References edit Thomas D Barbey R Surdin Kerjan Y June 1993 Evolutionary relationships between yeast and bacterial homoserine dehydrogenases FEBS Lett 323 3 289 93 doi 10 1016 0014 5793 93 81359 8 PMID 8500624 S2CID 23964791 Cami B Clepet C Patte JC 1993 Evolutionary comparisons of three enzymes of the threonine biosynthetic pathway among several microbial species Biochimie 75 6 487 95 doi 10 1016 0300 9084 93 90115 9 PMID 8395899 Ferreira RR Meinhardt LW Azevedo RA 2006 Lysine and threonine biosynthesis in sorghum seeds characterisation of aspartate kinase and homoserine dehydrogenase isoenzymes Ann Appl Biol 149 1 77 86 doi 10 1111 j 1744 7348 2006 00074 x a b c d DeLaBarre B Thompson PR Wright GD Berghuis AM March 2000 Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases Nat Struct Biol 7 3 238 44 doi 10 1038 73359 PMID 10700284 S2CID 26638309 a b Paris S Viemon C Curien G Dumas R February 2003 Mechanism of Control of Arabidopsis thaliana Aspartate Kinase Homoserine Dehydrogenase by Threonine J Biol Chem 278 7 5361 5366 doi 10 1074 jbc M207379200 PMID 12435751 a b c d e Schroeder AC Zhu C Yanamadala SR Cahoon RE Arkus KAJ Wachsstock L Bleeke J Krishnan HB Jez JM January 2010 Threonine insensitive Homoserine Dehydrogenase from Soybean Genomic Organization Kinetic Mechanism and in vivo Activity J Biol Chem 285 2 827 834 doi 10 1074 jbc M109 068882 PMC 2801284 PMID 19897476 a b Ghislain M Frankard V Vandenbossche D Matthews BF Jacobs M March 1994 Molecular analysis of the aspartate kinase homoserine dehydrogenase gene from Arabidopsis thaliana Plant Mol Biol 24 6 835 851 doi 10 1007 bf00014439 PMID 8204822 S2CID 6183867 a b Wedler FC Ley BW Shames SL Rembish SJ Kushmaul DL March 1992 Preferred order random kinetic mechanism for homoserine dehydrogenase of Escherichia coli Thr sensitive aspartokinase homoserine dehydrogenase I Equilibrium Isotope Exchange Kinetics Biochimica et Biophysica Acta BBA Protein Structure and Molecular Enzymology 1119 3 247 249 doi 10 1016 0167 4838 92 90209 v PMID 1547269 Jacques SL Nieman C Bareicha D Broadhead G Kinach R Honek JF Wright GD January 2001 Characterization of yeast homoserine dehydrogenase an antifungal target the invariant histidine 309 is important for enzyme integrity Biochimica et Biophysica Acta BBA Protein Structure and Molecular Enzymology 1544 1 2 28 41 doi 10 1016 S0167 4838 00 00203 X PMID 11341914 Wedler FC Ley BW March 1993 Kinetic and Regulatory Mechanisms for Escherichia coli Homoserine Dehydrogenase I Equilibrium Isotope Exchange Kinetics J Biol Chem 268 1 4880 4888 doi 10 1016 S0021 9258 18 53478 5 PMID 8444866 Azevedo RA 2002 Analysis of the aspartic acid metabolic pathway using mutant genes Amino Acids 22 3 217 230 doi 10 1007 s007260200010 PMID 12083066 S2CID 23327489 a b c Zhu Shimoni JX Galili G March 1998 Expression of an Arabidopsis Aspartate Kinase Homoserine Dehydrogenase Gene Is Metabolically Regulated by Photosynthesis Related Signals but Not by Nitrogenous Compounds Plant Physiol 116 3 1023 1028 doi 10 1104 pp 116 3 1023 PMC 35071 PMID 9501134 a b Zhu Shimoni JX Lev Yadun S Matthews B Calili C March 1997 Expression of an Aspartate Kinase Homoserine Dehydrogenase Gene IS Subject to Specific Spatial and Temporal Regulation in Vegetative Tissues Flowers and Developing Seeds Plant Physiol 113 3 695 706 doi 10 1104 pp 113 3 695 PMC 158187 PMID 12223636 Park SD Lee JY Sim SY Kim Y Lee HS July 2007 Characteristics of methionine production by an engineered Corynebacterium glutamicum strain Metab Eng 9 4 327 336 doi 10 1016 j ymben 2007 05 001 PMID 17604670 a b Bareich DC Nazi I Wright GD October 2003 Simultaneous In Vitro Assay of the First Four Enzymes in the Fungal Aspartate Pathway Identifies a New Class of Aspartate Kinase Inhibitor Chem Biol 10 10 967 973 doi 10 1016 j chembiol 2003 09 016 PMID 14583263 a b Yamaki H Yamaguchi M Tsuruo T Yamaguchi H May 1992 Mechanism of action of an antifungal antibiotich RI 331 S 2 amino 4 oxo 5 hydroxypentanoic acid kinetics of inactivation of homoserine dehydrogenase from Saccharomyces cerevisiae J Antibiot Tokyo 45 5 750 755 doi 10 7164 antibiotics 45 750 PMID 1352515 Jacques SL Mirza IA Ejim L Koteva K Hughes DW Green K Kinach R Honek JF Lai HK Berghuis AM Wright GD October 2003 Enzyme Assisted Suicide Molecular Basis for the Antifungal Activity of 5 Hydroxy 4 Oxonorvaline by Potent Inhibition of Homoserine Dehydrogenase Chem Biol 10 10 989 995 doi 10 1016 j chembiol 2003 09 015 PMID 14583265 Ejim L Mirza IA Capone C Nazi I Jenkins S Chee GL Berghui AM Wright GD July 2004 New phenolic inhibitors of yeast homoserine dehydrogenase Bioorg Med Chem 12 14 3825 3830 doi 10 1016 j bmc 2004 05 009 PMID 15210149 Further reading editBlack S Wright NG 1955 Homoserine dehydrogenase J Biol Chem 213 1 51 60 doi 10 1016 S0021 9258 18 71043 0 PMID 14353905 Starnes WL Munk P Maul SB Cunningham GN Cox DJ Shive W 1972 Threonine sensitive aspartokinase homoserine dehydrogenase complex amino acid composition molecular weight and subunit composition of the complex Biochemistry 11 5 677 87 doi 10 1021 bi00755a003 PMID 4551091 Veron M Falcoz Kelly F Cohen GN 1972 The threonine sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12 The two catalytic activities are carried by two independent regions of the polypeptide chain Eur J Biochem 28 4 520 7 doi 10 1111 j 1432 1033 1972 tb01939 x PMID 4562990 Portal nbsp Biology This article incorporates text from the public domain Pfam and InterPro IPR001342 Retrieved from https en wikipedia org w index php title Homoserine dehydrogenase amp oldid 1215901952, wikipedia, wiki, book, books, library,

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