Calibration of the dianionic phosphate group: Validation on the recognition site of the homodimeric enzyme phosphoglucose isomerase

SummaryA 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first autoantibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.

Download Full-text

Faculty Opinions recommendation of Responses of the central metabolism in Escherichia coli to phosphoglucose isomerase and glucose-6-phosphate dehydrogenase knockouts.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004114.210446 ◽

2004 ◽

Author(s):

Jacky Snoep

Keyword(s):

Escherichia Coli ◽

Phosphoglucose Isomerase ◽

Central Metabolism ◽

Glucose 6 Phosphate Dehydrogenase

Download Full-text

The effect of acceptor modification upon the synthesis of dinucleoside phosphates catalyzed by non-specific ribonucleases of Penicillium claviforme

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19790613 ◽

1979 ◽

Vol 44 (2) ◽

pp. 613-625 ◽

Cited By ~ 2

Author(s):

Valentina I. Gulyaeva ◽

Antonín Holý

Keyword(s):

Reaction Center ◽

Hydroxy Group ◽

Pyrimidine Ring ◽

Phosphate Group ◽

Mutual Orientation ◽

Acceptor Molecule ◽

Heterocyclic Base ◽

Sugar Moiety ◽

Cyclic Phosphate ◽

Penicillium Claviforme

The present paper studies the effect of the modification of heterocyclic base, sugar moiety and the presence of phosphate group on the nucleoside acceptors in the synthesis of dinucleoside phosphates from adenosine 2',3'-cyclic phosphate as donor, catalyzed by nonspecific acidic extracellular and intracellular ribonucleases from Penicillium claviforme. The enzyme binds specifically the acceptor molecule, preferring cytosine nucleosides. It requires the presence of the whole sugar moiety, an exact mutual orientation of the heterocyclic base and the reaction center (5'-hydroxy group), and a suitable conformation of the acceptor molecule. The enzyme-acceptor bond is homochiral and the presence of the N3-H group in the pyrimidine ring is important. The reaction between the donor and the acceptor is bimolecular and is competitively inhibited by some purine nucleosides.

Download Full-text

Balancing Selection on Electrophoretic Variation of Phosphoglucose Isomerase in Two Species of Field Cricket: Gryllus veletis and G. pennsylvanicus

Genetics ◽

10.1093/genetics/147.2.609 ◽

1997 ◽

Vol 147 (2) ◽

pp. 609-621

Author(s):

Laura A Katz ◽

Richard G Harrison

Keyword(s):

Balancing Selection ◽

Emergent Property ◽

Phosphoglucose Isomerase ◽

Field Cricket ◽

Nucleotide Variation ◽

Eastern United States ◽

Electrophoretic Variation ◽

Sympatric Populations ◽

Field Crickets ◽

Gryllus Veletis

Two species of crickets, Gryllus veletis and G. pennsylvanicus, share six electrophoretic mobility classes for the enzyme phosphoglucose isomerase (PGI), despite evidence from other genetic markers that the two species are not closely related within eastern North American field crickets. Moreover, the frequencies of the two most common PGI electrophoretic classes (PGI-100 and PGI-65) covary in sympatric populations of these species in the eastern United States, suggesting that PGI may be subject to trans-specific balancing selection. To determine the molecular basis of the electrophoretic variation, we characterized the DNA sequence of the Pgi gene from 29 crickets (15 G. veletis and 14 G. pennsylvanicus). Amino acid substitutions that distinguish the electrophoretic classes are not the same in the two species, and there is no evidence that specific replacement substitutions represent trans-specific polymorphism. In particular, the amino acids that diagnose the PGI-65 allele relative to the PGI-100 allele differ both between G. veletis and G. pennsylvanicus and within G. pennsylvanicus. The heterogeneity among electrophoretic classes that covary in sympatric populations coupled with analysis of patterns of nucleotide variation suggest that Pgi is not evolving neutrally. Instead, the data are consistent with balancing selection operating on an emergent property of the PGI protein.

Download Full-text