2007
DOI: 10.1021/bi0619270
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Human Glycinamide Ribonucleotide Transformylase:  Active Site Mutants as Mechanistic Probes

Abstract: Human glycinamide ribonucleotide transformylase (GART) (EC2.1.2.2) is a validated target for cancer chemotherapy, but mechanistic studies of this therapeutically important enzyme are limited. Site-directed mutagenesis, initial velocity studies, pH-rate studies, and substrate binding studies have been employed to probe the role of the strictly conserved active site residues, N106, H108, D144, and the semi-conserved K170 in substrate binding and catalysis. Only two conservative substitutions, N106Q and K170R, re… Show more

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Cited by 3 publications
(3 citation statements)
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“…In this case, significant differences between the human GART protein and the E. coli protein have been observed (Manieri et al, 2007). These studies suggest that study of the human (or mammalian) GART and GARS proteins are important for their accurate characterization, although clearly comparisons of the mammalian and bacterial proteins will be useful, as described below.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In this case, significant differences between the human GART protein and the E. coli protein have been observed (Manieri et al, 2007). These studies suggest that study of the human (or mammalian) GART and GARS proteins are important for their accurate characterization, although clearly comparisons of the mammalian and bacterial proteins will be useful, as described below.…”
Section: Discussionmentioning
confidence: 99%
“…The GART domain of the trifunctional GART gene has been cloned and expressed, allowing study of the GART monofunctional human protein. Structural and functional comparisons of the human and E. coli protein as well as targeted mutagenesis experiments have revealed important differences between these proteins (Manieri et al, 2007; Zhang et al, 2002). Similarly, structural and functional analysis coupled with targeted mutagenesis of the ADSL locus reveals important differences between the human, B. subtilis , and E. coli enzymes (Sivendran et al, 2004; Sivendran and Colman, 2008).…”
Section: Introductionmentioning
confidence: 99%
“…The crystal structures of Escherichia coli GART (Almassy et al, 1992;Chen et al, 1992;Klein et al, 1995;Greasley et al, 1999Greasley et al, , 2001, Mycobacterium tuberculosis GART (Zhang et al, 2009) and the human GART domain (Varney et al, 1997;Zhang et al, 2002Zhang et al, , 2003Dahms et al, 2005) have been determined. The catalytic mechanisms of GART have been studied in some detail (Caperelli & Giroux, 1997;Morikis et al, 2001;Su et al, 1998;Zhang et al, 2002;Manieri et al, 2007). GART is found as a single protein in prokaryotes, while in most eukaryotes it constitutes the C-terminal part of a monomeric but trifunctional protein with PurD-PurM-PurN activities (Almassy et al, 1992).…”
Section: Introductionmentioning
confidence: 99%