1q15: Difference between revisions

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[[Image:1q15.gif|left|200px]]<br /><applet load="1q15" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1q15.gif|left|200px]]<br /><applet load="1q15" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1q15, resolution 2.30Å" />

'''Carbapenam Synthetase'''<br />

==Overview==

Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that, catalyzes formation of the beta-lactam ring in, (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to, beta-lactam synthetase (beta-LS), which is involved in clavulanic acid, biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate, adenylation followed by beta-lactamization via a tetrahedral intermediate, or transition state. Another member of this family of ATP/Mg2+-dependent, enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather, than intramolecular, amide bond formation in asparagine biosynthesis. The, crystal structures of apo-CarA and CarA complexed with the substrate, (2S,5S)-5-carboxymethylproline (CMPr), ATP analog, alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+, ion have been determined. CarA forms a tetramer. Each monomer resembles, beta-LS and AS-B in overall fold, but key differences are observed. The, N-terminal domain lacks the glutaminase active site found in AS-B, and an, extended loop region not observed in beta-LS or AS-B is present., Comparison of the C-terminal synthetase active site to that in beta-LS, reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different, substrates of the two enzymes. The Mg2+ coordination is also different., Several key residues in the active site are conserved between CarA and, beta-LS, supporting proposed roles in beta-lactam formation. These data, provide further insight into the structures of this class of enzymes and, suggest that CarA might be a versatile target for protein engineering, experiments aimed at developing improved production methods and new, carbapenem antibiotics.

Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that catalyzes formation of the beta-lactam ring in (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to beta-lactam synthetase (beta-LS), which is involved in clavulanic acid biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate adenylation followed by beta-lactamization via a tetrahedral intermediate or transition state. Another member of this family of ATP/Mg2+-dependent enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather than intramolecular, amide bond formation in asparagine biosynthesis. The crystal structures of apo-CarA and CarA complexed with the substrate (2S,5S)-5-carboxymethylproline (CMPr), ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+ ion have been determined. CarA forms a tetramer. Each monomer resembles beta-LS and AS-B in overall fold, but key differences are observed. The N-terminal domain lacks the glutaminase active site found in AS-B, and an extended loop region not observed in beta-LS or AS-B is present. Comparison of the C-terminal synthetase active site to that in beta-LS reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different substrates of the two enzymes. The Mg2+ coordination is also different. Several key residues in the active site are conserved between CarA and beta-LS, supporting proposed roles in beta-lactam formation. These data provide further insight into the structures of this class of enzymes and suggest that CarA might be a versatile target for protein engineering experiments aimed at developing improved production methods and new carbapenem antibiotics.

==About this Structure==

1Q15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1Q15 OCA].

1Q15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q15 OCA].

==Reference==

Line 14:

[[Category: Single protein]]

[[Category: Gerratana, B.]]

[[Category: Miller, M.T.]]

[[Category: Miller, M T.]]

[[Category: Rosenzweig, A.C.]]

[[Category: Rosenzweig, A C.]]

[[Category: Stapon, A.]]

[[Category: Townsend, C.A.]]

[[Category: Townsend, C A.]]

[[Category: (2s]]

[[Category: 5s)-5-carboxymethylproline; b-ls]]

Line 28:

[[Category: n2-(carboxylmethyl)-l-arginine]]

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@@ Line 1: / Line 1: @@
-[[Image:1q15.gif|left|200px]]<br /><applet load="1q15" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1q15.gif|left|200px]]<br /><applet load="1q15" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1q15, resolution 2.30&Aring;" />
 '''Carbapenam Synthetase'''<br />
 ==Overview==
-Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that, catalyzes formation of the beta-lactam ring in, (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to, beta-lactam synthetase (beta-LS), which is involved in clavulanic acid, biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate, adenylation followed by beta-lactamization via a tetrahedral intermediate, or transition state. Another member of this family of ATP/Mg2+-dependent, enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather, than intramolecular, amide bond formation in asparagine biosynthesis. The, crystal structures of apo-CarA and CarA complexed with the substrate, (2S,5S)-5-carboxymethylproline (CMPr), ATP analog, alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+, ion have been determined. CarA forms a tetramer. Each monomer resembles, beta-LS and AS-B in overall fold, but key differences are observed. The, N-terminal domain lacks the glutaminase active site found in AS-B, and an, extended loop region not observed in beta-LS or AS-B is present., Comparison of the C-terminal synthetase active site to that in beta-LS, reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different, substrates of the two enzymes. The Mg2+ coordination is also different., Several key residues in the active site are conserved between CarA and, beta-LS, supporting proposed roles in beta-lactam formation. These data, provide further insight into the structures of this class of enzymes and, suggest that CarA might be a versatile target for protein engineering, experiments aimed at developing improved production methods and new, carbapenem antibiotics.
+Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that catalyzes formation of the beta-lactam ring in (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to beta-lactam synthetase (beta-LS), which is involved in clavulanic acid biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate adenylation followed by beta-lactamization via a tetrahedral intermediate or transition state. Another member of this family of ATP/Mg2+-dependent enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather than intramolecular, amide bond formation in asparagine biosynthesis. The crystal structures of apo-CarA and CarA complexed with the substrate (2S,5S)-5-carboxymethylproline (CMPr), ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+ ion have been determined. CarA forms a tetramer. Each monomer resembles beta-LS and AS-B in overall fold, but key differences are observed. The N-terminal domain lacks the glutaminase active site found in AS-B, and an extended loop region not observed in beta-LS or AS-B is present. Comparison of the C-terminal synthetase active site to that in beta-LS reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different substrates of the two enzymes. The Mg2+ coordination is also different. Several key residues in the active site are conserved between CarA and beta-LS, supporting proposed roles in beta-lactam formation. These data provide further insight into the structures of this class of enzymes and suggest that CarA might be a versatile target for protein engineering experiments aimed at developing improved production methods and new carbapenem antibiotics.
 ==About this Structure==
-Q15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q15 OCA].
+Q15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pectobacterium_carotovorum Pectobacterium carotovorum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q15 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Gerratana, B.]]
-[[Category: Miller, M.T.]]
+[[Category: Miller, M T.]]
-[[Category: Rosenzweig, A.C.]]
+[[Category: Rosenzweig, A C.]]
 [[Category: Stapon, A.]]
-[[Category: Townsend, C.A.]]
+[[Category: Townsend, C A.]]
 [[Category: (2s]]
 [[Category: 5s)-5-carboxymethylproline; b-ls]]
@@ Line 28: / Line 28: @@
 [[Category: n2-(carboxylmethyl)-l-arginine]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 03:22:58 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:43 2008''