The arsonomethyl group as an analogue of phosphate. An X-ray investigation

Abstract

The X-ray structure analysis of three compounds of interest as enzyme substrates is reported. They are the hydrated forms of (I) DL-2-amino-4-arsonobutanoic acid [HO-AsO2--CH2-CH2-CH(NH3+)-CO2H], (II) DL-2-amino-4-phosphonobutanoic acid [HO-PO2--CH2-CH2-CH(NH3+)-CO2H] and the hydrated barium salt of (III) D-3-phosphoglycerate [HO-PO2--O-CH2-CH(OH)-CO2-]. The structures were fully refined to R factors of 0.033, 0.053 and 0.046. For the compounds (I) and (II) the charge distribution was directly determined by locating all H atoms. The co-ordination around As and P is approximately tetrahedral, with the valency angle between the two charged O atoms enlarged to 112 degrees in compound (I), 166 degrees in compound (II) and 122 degrees in compound (III). The As-X bond distances are increased relative to P-X to accommodate the increased atomic radius. The analysis establishes that the compounds are structural analogues. Tables of co-ordinates for H atoms, anisotropic thermal parameters, bond lengths and bond angles for the three compounds have been deposited as Supplementary Publication SUP 50122 (5 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained directly [see Biochem J. (1983) 209, 5].

Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom

“…However, 2-arsonoacetyl-L-proline was found to be over 2000-fold weaker an inhibitor than 2-phosphonoacetyl-L-proline. The As-C and As-O bond distances in the former are significantly longer than the P-C and P-O distances in the latter (compare DL-2-amino-4-arsonobutanoic acid and DL-2-amino-4-phosphonobutanoic acid; Kamiya et al, .-1983). These greater bond distances may place an arsenic oxygen atom too far to the left of the active-site zinc atom in angiotensin-converting enzyme (see Fig.…”

Pentavalent Arsenate Transport by Zebrafish Phosphate Transporter NaPi-IIb1

“…As V shares high chemical similarity to phosphate, as they are both tetrahedral molecules found in group Va of the periodic table and they share three similar dissociation constants. 9,10 The pK a values of arsenic acid (AsO(OH) 3 ) are 2.26, 6.76, and 11.29, and that of phosphoric acid (PO(OH) 3 ) are 2.16, 7.21, and 12.32. 9 Because of the structural similarity between As V and phosphate, As V is a well-known competitive inhibitor of enzymes that involve phosphate, such as glyceraldehyde-3-phosphate dehydrogenase, as well as the sodium pump and anion exchanger in human erythrocytes.…”

“…9,10 The pK a values of arsenic acid (AsO(OH) 3 ) are 2.26, 6.76, and 11.29, and that of phosphoric acid (PO(OH) 3 ) are 2.16, 7.21, and 12.32. 9 Because of the structural similarity between As V and phosphate, As V is a well-known competitive inhibitor of enzymes that involve phosphate, such as glyceraldehyde-3-phosphate dehydrogenase, as well as the sodium pump and anion exchanger in human erythrocytes. 9,11 As V additionally uncouples oxidative phosphorylation by substituting phosphate in ATP, leading to the formation of ADP-arsenate.…”

“…9 Because of the structural similarity between As V and phosphate, As V is a well-known competitive inhibitor of enzymes that involve phosphate, such as glyceraldehyde-3-phosphate dehydrogenase, as well as the sodium pump and anion exchanger in human erythrocytes. 9,11 As V additionally uncouples oxidative phosphorylation by substituting phosphate in ATP, leading to the formation of ADP-arsenate. 12 Although As V is generally considered less toxic than other species of arsenic, it undergoes a series of reductions and methylations upon entering the cell, which lead to the generation of other more toxic species such as inorganic As III as well as organic monomethyl or dimethyl metabolites and therefore amplified toxicity.…”

Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

“…One of these sites is the [3H]AP4 binding site (Butcher et a!., 1983;Monaghan et al, 1983;Bridges et al, 1986), which appears to be the same as the chloride-and calcium-sensitive [ 3H]G1u binding site (Monaghan et at., (Kamiya et al, 1983) shown in two orthogonal views. Note the very similar orientation of all atoms, in particular, the charged amino, carboxyl, and phosphate (L-PSer) or phosphonate (L-AP4) group.…”