Escherichia coli serine hydroxymethyltransferase. The role of histidine 228 in determining reaction specificity.

Zamora, Magdalena; Shostak, Keith; Gautam-Basak, Mamta; Schirch, Verne

doi:10.1016/s0021-9258(19)37096-6

Cited by 42 publications

(11 citation statements)

References 31 publications

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“…In the absence of an X-ray crystal structure, past studies have been performed by chemical modification and site-directed mutagenesis based on amino acid residues that are totally conserved across the known SHMT protein sequences. Much of this work has concentrated on the dimeric enzyme from Escherichia coli [18][19][20][21][22] and on the tetrameric sheep liver enzyme [23,24].…”

Section: Figurementioning

confidence: 99%

The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy

1998

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The crystal structure shows the evolutionary relationship between SHMT and other alpha class PLP-dependent enzymes, as the fold is highly conserved. Many of the results of site-directed mutagenesis studies can easily be rationalised or re-interpreted in light of the structure presented here. For example, His 151 is not the catalytic base, contrary to the findings of others. A mechanism for the cleavage of serine to glycine and formaldehyde is proposed.

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Section: Figurementioning

confidence: 99%

The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy

1998

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“…The glycine-dependent aldolases are pyridoxal 5-phosphate-dependent enzymes which catalyze the reversible aldol reaction of glycine with an aldehyde acceptor to form a β-hydroxy-α-amino acid …”

Section: Glycine-dependent Aldolasesmentioning

confidence: 99%

“…In vivo SHMT (EC 2.1.2.1) catalyzes the reversible aldol reaction between glycine and formaldehyde to give l -serine. For this reaction the cofactor tetrahydrofolate (THF) is required, which binds nonenzymatically with formaldehyde to form N 5 , N 10 -methylenetetrahydrofolate which is then accepted by the enzyme 125a…”

Section: Glycine-dependent Aldolasesmentioning

confidence: 99%

Recent Advances in the Chemoenzymatic Synthesis of Carbohydrates and Carbohydrate Mimetics

et al. 1996

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ContentsI. General Introduction 443 II. Aldol Addition with Aldolases 443 1. Introduction 443 2. DHAP-Dependent Aldolases 447 2.1. General Background 447 2.2. Synthetic Applications 449 3. Pyruvate-and Phosphoenolpyruvate-Dependent Aldolases 453 3.1. N-Acetylneuraminic Acid Aldolase and NeuAc Synthetase 453 3.2. 3-Deoxy-D-manno-2-octulosonate (KDO) Aldolase and 3-Deoxy-D-manno-2-octulosonate 8-Phosphate (KDO-8-P) Synthetase 456 3.3. Other Pyruvate-and Phosphoenolpyruvate-Dependent Aldolases 457 4. 2-Deoxyribose-5-phosphate Aldolase 457 5. Glycine-Dependent Aldolases 459 III. Enzymatic Glycosidation 460 1. Glycosidases and Transglycosidases 460 2. Glycosyltransferases 462 2.1. Non-Leloir Glycosyltransferases 462 2.2. Leloir-type Glycosyltransferases 463 IV. Concluding Remarks 469 V. References 469

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“…There are few well-characterized examples of hydroxymethyltransferases, with serine hydroxymethyltransferase being the most thoroughly studied ( − ). This enzyme contains PLP and, after transimination with l -serine, catalyzes the cleavage of the Cα−Cβ bond to generate formaldehyde and glycine.…”

mentioning

confidence: 99%

Mycobacterium tuberculosis Ketopantoate Hydroxymethyltransferase: Tetrahydrofolate-Independent Hydroxymethyltransferase and Enolization Reactions with α-Keto Acids

Sugantino

Zheng

et al. 2002

Biochemistry

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The panB gene that encodes ketopantoate hydroxymethyltransferase has been cloned from Mycobacterium tuberculosis, expressed, and purified to homogeneity. 1H NMR spectroscopy was used to determine the rate of (i) tetrahydrofolate-independent hydroxymethyltransferase chemistry between formaldehyde and alpha-ketoisovalerate and (ii) deuterium exchange in the methylenetetrahydrofolate-independent enolization of alpha-ketoisovalerate and other alpha-keto acids, catalyzed by PanB. These studies have demonstrated that substrate enolization by PanB is divalent metal-dependent with a preference of Mg2+ > Zn2+ > Co2+ > Ni2+ > Ca2+. The rate of enolization is pH-dependent with optimal activity in the range of 7.0-7.5. The pH profile was bell-shaped, depending on the ionization state of two ionizable groups with apparent pK values of 6.2 and 8.3. Enolization and isotope exchange occurs with some alpha-keto acids (e.g., pyruvate and alpha-ketobutyrate), resulting in the complete exchange of all beta-hydrogens. Enzyme-catalyzed enolization and isotope exchange occur with other long-chain and branched alpha-keto acids, resulting in the stereospecific exchange of only one of the beta-hydrogen atoms. These results are discussed in the context of steric restrictions present in the enzyme active site and the stereochemistry of base-catalyzed isotope exchange.

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Escherichia coli serine hydroxymethyltransferase. The role of histidine 228 in determining reaction specificity.

Cited by 42 publications

References 31 publications

The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy

The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy

Recent Advances in the Chemoenzymatic Synthesis of Carbohydrates and Carbohydrate Mimetics

Mycobacterium tuberculosis Ketopantoate Hydroxymethyltransferase: Tetrahydrofolate-Independent Hydroxymethyltransferase and Enolization Reactions with α-Keto Acids

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