1fuo: Difference between revisions

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FUMARASE C WITH BOUND CITRATE

OverviewOverview

Fumarase C catalyzes the stereospecific interconversion of fumarate to L-malate as part of the metabolic citric acid or Kreb's cycle. The recent three-dimensional structure of fumarase C from Escherichia coli has identified a binding site for anions which is generated by side chains from three of the four subunits within the tetramer (Weaver et al., 1995). These same side chains are found in the three most highly conserved regions within the class II fumarase superfamily. The site was initially characterized by crystallographic studies through the binding of a heavy atom derivative, tungstate. A number of additional crystallographic structures using fumarase crystals with bound inhibitors and poor substrates have now been studied. The new structures have both confirmed the originally proposed active site, site A, and led to the discovery of a novel second binding site that is structurally nearby, site B. Site A utilizes a combination of residues, including H188, T187, K324, N326, T100, N141, S139, and S140, to form direct hydrogen bonds to each of the inhibitors. The A-site has been demonstrated by studying crystalline fumarase with the bound competitive inhibitors-citrate and 1,2,4,5-benzenetetracarboxylic acid. The crystal structure of fumarase C with beta-(trimethylsilyl)maleate, a cis substrate for fumarase, has led to the discovery of the second site or B-site. Sites A and B have different properties in terms of their three-dimensional structures. Site B, for example, is formed by atoms from only one of the subunits within the tetramer and mainly by atoms from a pi-helix between residues H129 through N135. The crystal structures show that the two locations are separated by approximately 12 A. A highly coordinated buried water molecule is also found at the active or A-site. The high-resolution crystal structures describe both sites, and atoms near the A-site are used to propose a likely enzyme/substrate complex.

About this StructureAbout this Structure

1FUO is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Fumarate hydratase, with EC number 4.2.1.2 Full crystallographic information is available from OCA.

ReferenceReference

Crystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli., Weaver T, Banaszak L, Biochemistry. 1996 Nov 5;35(44):13955-65. PMID:8909293

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 '''FUMARASE C WITH BOUND CITRATE'''<br />
 ==Overview==
-Fumarase C catalyzes the stereospecific interconversion of fumarate to, L-malate as part of the metabolic citric acid or Kreb's cycle. The recent, three-dimensional structure of fumarase C from Escherichia coli has, identified a binding site for anions which is generated by side chains, from three of the four subunits within the tetramer (Weaver et al., 1995)., These same side chains are found in the three most highly conserved, regions within the class II fumarase superfamily. The site was initially, characterized by crystallographic studies through the binding of a heavy, atom derivative, tungstate. A number of additional crystallographic, structures using fumarase crystals with bound inhibitors and poor, substrates have now been studied. The new structures have both confirmed, the originally proposed active site, site A, and led to the discovery of a, novel second binding site that is structurally nearby, site B. Site A, utilizes a combination of residues, including H188, T187, K324, N326, T100, N141, S139, and S140, to form direct hydrogen bonds to each of the, inhibitors. The A-site has been demonstrated by studying crystalline, fumarase with the bound competitive inhibitors-citrate and, 1,2,4,5-benzenetetracarboxylic acid. The crystal structure of fumarase C, with beta-(trimethylsilyl)maleate, a cis substrate for fumarase, has led, to the discovery of the second site or B-site. Sites A and B have, different properties in terms of their three-dimensional structures. Site, B, for example, is formed by atoms from only one of the subunits within, the tetramer and mainly by atoms from a pi-helix between residues H129, through N135. The crystal structures show that the two locations are, separated by approximately 12 A. A highly coordinated buried water, molecule is also found at the active or A-site. The high-resolution, crystal structures describe both sites, and atoms near the A-site are used, to propose a likely enzyme/substrate complex.
+Fumarase C catalyzes the stereospecific interconversion of fumarate to L-malate as part of the metabolic citric acid or Kreb's cycle. The recent three-dimensional structure of fumarase C from Escherichia coli has identified a binding site for anions which is generated by side chains from three of the four subunits within the tetramer (Weaver et al., 1995). These same side chains are found in the three most highly conserved regions within the class II fumarase superfamily. The site was initially characterized by crystallographic studies through the binding of a heavy atom derivative, tungstate. A number of additional crystallographic structures using fumarase crystals with bound inhibitors and poor substrates have now been studied. The new structures have both confirmed the originally proposed active site, site A, and led to the discovery of a novel second binding site that is structurally nearby, site B. Site A utilizes a combination of residues, including H188, T187, K324, N326, T100, N141, S139, and S140, to form direct hydrogen bonds to each of the inhibitors. The A-site has been demonstrated by studying crystalline fumarase with the bound competitive inhibitors-citrate and 1,2,4,5-benzenetetracarboxylic acid. The crystal structure of fumarase C with beta-(trimethylsilyl)maleate, a cis substrate for fumarase, has led to the discovery of the second site or B-site. Sites A and B have different properties in terms of their three-dimensional structures. Site B, for example, is formed by atoms from only one of the subunits within the tetramer and mainly by atoms from a pi-helix between residues H129 through N135. The crystal structures show that the two locations are separated by approximately 12 A. A highly coordinated buried water molecule is also found at the active or A-site. The high-resolution crystal structures describe both sites, and atoms near the A-site are used to propose a likely enzyme/substrate complex.
 ==About this Structure==
-FUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MLT and CIT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FUO OCA].
+FUO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MLT:'>MLT</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FUO OCA].
 ==Reference==
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 [[Category: tricarboxylic acid cycle]]
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