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1 SHMT also catalyzes the folate-independent retroaldol cl
2 SHMT catalyses interconversion of serine and glycine whi
3 SHMT enzymes are the major source of the one-carbon unit
4 SHMT is a pyridoxal 5'-phosphate-dependent enzyme that c
5 SHMT is crucial for deoxythymidylate biosynthesis and a
6 SHMT is involved in the penultimate step of thymidylate
7 SHMT is present in eukaryotic cells as mitochondrial SHM
8 SHMT requires both pyridoxal phosphate (PLP) and tetrahy
9 SHMT tetramers have surface charge distributions which s
10 SHMTs are emerging as a promising target for development
13 ves incubating [2-3H]glycine, H4PteGlun, and SHMT for 3 min followed by a separation of the exchanged
15 alciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based a
16 ed into a rapid and sensitive assay for both SHMT and H4PteGlun and the one-carbon derivatives of H4P
22 es cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM
23 e of the inactive form of murine cytoplasmic SHMT (cSHMT), lacking only the polyglutamate tail of the
24 ture at 2.8 A resolution of rabbit cytosolic SHMT (rcSHMT) in two forms: one with the PLP covalently
26 site mutant homotetrameric rabbit cytosolic SHMTs identified lysine residues that contribute to the
28 ted by a futile cycle comprising the enzymes SHMT and 5,10-methenyltetrahydrofolate synthetase (MTHFS
31 n donor formate generally rescues cells from SHMT inhibition, but paradoxically increases the inhibit
32 ure closely resembles the structure of human SHMT, confirming its similarity to the alpha-class of PL
33 r measuring serine hydroxymethyltransferase (SHMT) activity toward formation of serine and (6S)-H(4)P
35 activity of serine hydroxymethyltransferase (SHMT) and strongly inhibits SHMT and other folate-depend
42 MTHFD1) and serine hydroxymethyltransferase (SHMT) generate 5,10-methylenetetrahydrofolate for de nov
45 Mammalian serine hydroxymethyltransferase (SHMT) is a tetrameric, pyridoxal phosphate-dependent enz
47 richia coli serine hydroxymethyltransferase (SHMT) showed that the final rate determining folding ste
48 r cytosolic serine hydroxymethyltransferase (SHMT) were determined by a combination of isothermal tit
49 se (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine beta-synthase (CBS) genes and t
50 tochondrial serine hydroxymethyltransferase (SHMT), combined with glycine decarboxylase, catalyzes an
51 the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stabilit
52 theless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient i
53 the enzymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate re
54 nhibitor of serine hydroxymethyltransferase (SHMT), was enriched in nuclei, accounting for 35% of fol
57 abolized by serine hydroxymethyltransferase (SHMT)2 in the mitochondria and generates glycine and C1
58 hat targets serine hydroxymethyltransferase (SHMT)2 in the mitochondria and SHMT1 and de novo purine
60 cytosolic serine hydroxymethyltransferases (SHMT) confirmed their close similarity in tertiary and d
61 ne or both serine hydroxymethyltransferases (SHMT) or at the genes encoding one or both methylenetetr
63 The enzyme serine hydroxymethyltransferse (SHMT) converts serine into glycine and a tetrahydrofolat
64 midylate (dTMP) synthesis through changes in SHMT expression is causative in folate-responsive NTDs.
65 se data establish that 5-CHO-THF can inhibit SHMT in vivo and thereby influence glycine pool size.
68 -CHO-THF was undetectable in strains lacking SHMT activity, confirming SHMT as the in vivo source of
69 first structure of a ligand-bound mammalian SHMT allows identification of amino acid residues involv
71 is mitochondrial in plants and mitochondrial SHMT is central to photorespiration, we examined the imp
72 present in eukaryotic cells as mitochondrial SHMT and cytoplasmic (cSHMT) isozymes that are encoded b
74 gnated shm1-1) is defective in mitochondrial SHMT activity and displays a lethal photorespiratory phe
77 and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units
79 When grown on glycine, the mitochondrial SHMT was the predominant isozyme catalyzing the synthesi
81 both a Gly and Ala residue, and each mutant SHMT was purified and characterized with respect to kine
84 xplaining previous observations that nuclear SHMT is not a robust source of one-carbons for de novo d
85 bes the purification and characterization of SHMT from the thermophilic organism Sulfolobus solfatari
86 xploit antifolate scaffold in development of SHMT inhibitors because it seems likely that especially
88 in maintaining the structure and function of SHMT and a possible role in pyridoxal 5'-phosphate addit
93 ns the properties of several site mutants of SHMT and offers testable hypotheses for a more detailed
94 Studies of wild-type and site mutants of SHMT have failed to clearly establish the mechanism of t
95 upplemented media indicated that the role of SHMT in the KinB pathway is to feed the pool of C1 units
97 ation significantly changed the structure of SHMT, the spectral properties of its complexes, or the k
99 that only two of the four catalytic sites on SHMT are catalytically competent and that the cSHMT-glyc
100 s and complex formation for photorespiratory SHMT activity demonstrates more complicated regulation o
102 a pyrazolopyran scaffold that inhibits plant SHMT, we identify small-molecule dual inhibitors of huma
104 tal structures of MTX and PTX bound to plant SHMT isozymes from cytosol and mitochondria-human isozym
105 um falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified
106 co-localization of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, in
107 n 6 genes (MTHFR, MTRR, FOLH1, CbetaS, RFC1, SHMT) involved in folate absorption and metabolism were
108 adiation employ the single hit multi-target (SHMT) algorithm, which yields a single value, the D0, as
109 nism for previous studies demonstrating that SHMT expression is rate-limiting for de novo thymidylate
110 thase to the nuclear lamina, indicating that SHMT serves as scaffold protein that is essential for co
112 s work presents a comprehensive study of the SHMT gene family members, including synteny, phylogeny,
113 Mapping of the identified mutations onto the SHMT structural model uncovered key residues for structu
115 THF levels do not much affect fluxes through SHMT or any other folate-dependent reaction, i.e. that 5
116 tive inhibitors of 5-CHO-H4PteGlu binding to SHMT, showing that anions compete for the polyglutamate
118 ives of 5-CHO-H4PteGlun were cross-linked to SHMT by a carbodiimide reaction to Lys-450 which resides
120 our human serine hydroxymethyl transferase (SHMT) 2 and glycinamide ribonucleotide formyltransferase
122 to investigate the contributions of the two SHMT isozymes to the production of glycine and one-carbo