1s3i: Difference between revisions

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[[Image:1s3i.jpg|left|200px]]<br /><applet load="1s3i" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1s3i.jpg|left|200px]]<br /><applet load="1s3i" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1s3i, resolution 2.30Å" />

'''Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase'''<br />

==Overview==

10-Formyltetrahydrofolate dehydrogenase (FDH) converts, 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to, tetrahydrofolate. The protein comprises two functional domains: a, hydrolase domain that removes a formyl group from, 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain, that reduces the formyl to carbon dioxide. As a first step toward, deciphering the catalytic mechanism of the enzyme, we have determined the, crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A, resolution. The structure comprises two domains. As expected, domain 1, shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide, formyltransferase, but, unexpectedly, the structural similarity between, the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and, methionyl-tRNA-formyltransferase extends to the C terminus of both, proteins. The active site contains a molecule of beta-mercaptoethanol that, is positioned between His-106 and Asp-142 and that appears to mimic the, formate product. We propose a catalytic mechanism for the hydrolase, reaction in which Asp-142 polarizes the catalytic water molecule and, His-106 orients the carbonyl group of formyl. The structure also provides, clues as to how, in the native enzyme, the hydrolase domain transfers its, product to the dehydrogenase domain.

10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein comprises two functional domains: a hydrolase domain that removes a formyl group from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that reduces the formyl to carbon dioxide. As a first step toward deciphering the catalytic mechanism of the enzyme, we have determined the crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure comprises two domains. As expected, domain 1 shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide formyltransferase, but, unexpectedly, the structural similarity between the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA-formyltransferase extends to the C terminus of both proteins. The active site contains a molecule of beta-mercaptoethanol that is positioned between His-106 and Asp-142 and that appears to mimic the formate product. We propose a catalytic mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic water molecule and His-106 orients the carbonyl group of formyl. The structure also provides clues as to how, in the native enzyme, the hydrolase domain transfers its product to the dehydrogenase domain.

==About this Structure==

1S3I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with BME as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1S3I OCA].

1S3I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S3I OCA].

==Reference==

Line 14:

[[Category: Rattus norvegicus]]

[[Category: Single protein]]

[[Category: Chumanevich, A.A.]]

[[Category: Chumanevich, A A.]]

[[Category: Davies, C.]]

[[Category: Krupenko, S.A.]]

[[Category: Krupenko, S A.]]

[[Category: BME]]

[[Category: rossmann fold]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:35 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1s3i.jpg|left|200px]]<br /><applet load="1s3i" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1s3i.jpg|left|200px]]<br /><applet load="1s3i" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1s3i, resolution 2.30&Aring;" />
 '''Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase'''<br />
 ==Overview==
--Formyltetrahydrofolate dehydrogenase (FDH) converts, 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to, tetrahydrofolate. The protein comprises two functional domains: a, hydrolase domain that removes a formyl group from, 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain, that reduces the formyl to carbon dioxide. As a first step toward, deciphering the catalytic mechanism of the enzyme, we have determined the, crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A, resolution. The structure comprises two domains. As expected, domain 1, shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide, formyltransferase, but, unexpectedly, the structural similarity between, the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and, methionyl-tRNA-formyltransferase extends to the C terminus of both, proteins. The active site contains a molecule of beta-mercaptoethanol that, is positioned between His-106 and Asp-142 and that appears to mimic the, formate product. We propose a catalytic mechanism for the hydrolase, reaction in which Asp-142 polarizes the catalytic water molecule and, His-106 orients the carbonyl group of formyl. The structure also provides, clues as to how, in the native enzyme, the hydrolase domain transfers its, product to the dehydrogenase domain.
+-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein comprises two functional domains: a hydrolase domain that removes a formyl group from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that reduces the formyl to carbon dioxide. As a first step toward deciphering the catalytic mechanism of the enzyme, we have determined the crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure comprises two domains. As expected, domain 1 shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide formyltransferase, but, unexpectedly, the structural similarity between the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA-formyltransferase extends to the C terminus of both proteins. The active site contains a molecule of beta-mercaptoethanol that is positioned between His-106 and Asp-142 and that appears to mimic the formate product. We propose a catalytic mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic water molecule and His-106 orients the carbonyl group of formyl. The structure also provides clues as to how, in the native enzyme, the hydrolase domain transfers its product to the dehydrogenase domain.
 ==About this Structure==
-S3I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with BME as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S3I OCA].
+S3I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S3I OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Rattus norvegicus]]
 [[Category: Single protein]]
-[[Category: Chumanevich, A.A.]]
+[[Category: Chumanevich, A A.]]
 [[Category: Davies, C.]]
-[[Category: Krupenko, S.A.]]
+[[Category: Krupenko, S A.]]
 [[Category: BME]]
 [[Category: rossmann fold]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:04:26 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:35 2008''