4jdw

From Proteopedia

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Current revision

CRYSTAL STRUCTURE AND MECHANISM OF L-ARGININE: GLYCINE AMIDINOTRANSFERASE: A MITOCHONDRIAL ENZYME INVOLVED IN CREATINE BIOSYNTHESIS

Structural highlights

4jdw is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GATM_HUMAN Defects in GATM are the cause of arginine:glycine amidinotransferase deficiency (AGAT deficiency) [MIM:612718. AGAT deficiency is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain.

Function

GATM_HUMAN Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

L-arginine:glycine amidinotransferase (AT) catalyses the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the immediate precursor of creatine. We have determined the crystal structure of the recombinant human enzyme by multiple isomorphous replacement at 1.9 A resolution. A telluromethionine derivative was used in sequence assignment. The structure of AT reveals a new fold with 5-fold pseudosymmetry of circularly arranged betabeta alphabeta-modules. These enclose the active site compartment, which is accessible only through a narrow channel. The overall structure resembles a basket with handles that are formed from insertions into the betabeta alphabeta-modules. Binding of L-ornithine, a product inhibitor, reveals a marked induced-fit mechanism, with a loop at the active site entrance changing its conformation accompanied by a shift of an alpha-helix by -4 A. Binding of the arginine educt to the inactive mutant C407A shows a similar mode of binding. A reaction mechanism with a catalytic triad Cys-His-Asp is proposed on the basis of substrate and product bound states.

Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.,Humm A, Fritsche E, Steinbacher S, Huber R EMBO J. 1997 Jun 16;16(12):3373-85. PMID:9218780^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cullen ME, Yuen AH, Felkin LE, Smolenski RT, Hall JL, Grindle S, Miller LW, Birks EJ, Yacoub MH, Barton PJ. Myocardial expression of the arginine:glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation. 2006 Jul 4;114(1 Suppl):I16-20. PMID:16820567 doi:10.1161/CIRCULATIONAHA.105.000448
↑ McMinn J, Wei M, Schupf N, Cusmai J, Johnson EB, Smith AC, Weksberg R, Thaker HM, Tycko B. Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. Placenta. 2006 Jun-Jul;27(6-7):540-9. Epub 2005 Aug 24. PMID:16125225 doi:10.1016/j.placenta.2005.07.004
↑ Monk D, Arnaud P, Apostolidou S, Hills FA, Kelsey G, Stanier P, Feil R, Moore GE. Limited evolutionary conservation of imprinting in the human placenta. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6623-8. Epub 2006 Apr 13. PMID:16614068 doi:10.1073/pnas.0511031103
↑ Humm A, Fritsche E, Steinbacher S, Huber R. Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. EMBO J. 1997 Jun 16;16(12):3373-85. PMID:9218780 doi:10.1093/emboj/16.12.3373

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4jdw"

@@ Line 1: / Line 1: @@
-[[Image:4jdw.jpg|left|200px]]<br /><applet load="4jdw" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="4jdw, resolution 2.50&Aring;" />
-'''CRYSTAL STRUCTURE AND MECHANISM OF L-ARGININE: GLYCINE AMIDINOTRANSFERASE: A MITOCHONDRIAL ENZYME INVOLVED IN CREATINE BIOSYNTHESIS'''<br />
-==Overview==
+==CRYSTAL STRUCTURE AND MECHANISM OF L-ARGININE: GLYCINE AMIDINOTRANSFERASE: A MITOCHONDRIAL ENZYME INVOLVED IN CREATINE BIOSYNTHESIS==
-L-arginine:glycine amidinotransferase (AT) catalyses the committed step in, creatine biosynthesis by formation of guanidinoacetic acid, the immediate, precursor of creatine. We have determined the crystal structure of the, recombinant human enzyme by multiple isomorphous replacement at 1.9 A, resolution. A telluromethionine derivative was used in sequence, assignment. The structure of AT reveals a new fold with 5-fold, pseudosymmetry of circularly arranged betabeta alphabeta-modules. These, enclose the active site compartment, which is accessible only through a, narrow channel. The overall structure resembles a basket with handles that, are formed from insertions into the betabeta alphabeta-modules. Binding of, L-ornithine, a product inhibitor, reveals a marked induced-fit mechanism, with a loop at the active site entrance changing its conformation, accompanied by a shift of an alpha-helix by -4 A. Binding of the arginine, educt to the inactive mutant C407A shows a similar mode of binding. A, reaction mechanism with a catalytic triad Cys-His-Asp is proposed on the, basis of substrate and product bound states.
+<StructureSection load='4jdw' size='340' side='right'caption='[[4jdw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4jdw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JDW FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jdw OCA], [https://pdbe.org/4jdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jdw RCSB], [https://www.ebi.ac.uk/pdbsum/4jdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jdw ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/GATM_HUMAN GATM_HUMAN] Defects in GATM are the cause of arginine:glycine amidinotransferase deficiency (AGAT deficiency) [MIM:[https://omim.org/entry/612718 612718]. AGAT deficiency is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain.
+== Function ==
+[https://www.uniprot.org/uniprot/GATM_HUMAN GATM_HUMAN] Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.<ref>PMID:16820567</ref> <ref>PMID:16125225</ref> <ref>PMID:16614068</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jd/4jdw_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4jdw ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+L-arginine:glycine amidinotransferase (AT) catalyses the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the immediate precursor of creatine. We have determined the crystal structure of the recombinant human enzyme by multiple isomorphous replacement at 1.9 A resolution. A telluromethionine derivative was used in sequence assignment. The structure of AT reveals a new fold with 5-fold pseudosymmetry of circularly arranged betabeta alphabeta-modules. These enclose the active site compartment, which is accessible only through a narrow channel. The overall structure resembles a basket with handles that are formed from insertions into the betabeta alphabeta-modules. Binding of L-ornithine, a product inhibitor, reveals a marked induced-fit mechanism, with a loop at the active site entrance changing its conformation accompanied by a shift of an alpha-helix by -4 A. Binding of the arginine educt to the inactive mutant C407A shows a similar mode of binding. A reaction mechanism with a catalytic triad Cys-His-Asp is proposed on the basis of substrate and product bound states.
-==Disease==
+Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.,Humm A, Fritsche E, Steinbacher S, Huber R EMBO J. 1997 Jun 16;16(12):3373-85. PMID:9218780<ref>PMID:9218780</ref>
-Known diseases associated with this structure: AGAT deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602360 602360]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-JDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ARG:'>ARG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycine_amidinotransferase Glycine amidinotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.4.1 2.1.4.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JDW OCA].
+</div>
+<div class="pdbe-citations 4jdw" style="background-color:#fffaf0;"></div>
-==Reference==
+== References ==
-Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis., Humm A, Fritsche E, Steinbacher S, Huber R, EMBO J. 1997 Jun 16;16(12):3373-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9218780 9218780]
+<references/>
-[[Category: Glycine amidinotransferase]]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Fritsche, E.]]
+[[Category: Fritsche E]]
-[[Category: Huber, R.]]
+[[Category: Huber R]]
-[[Category: Humm, A.]]
+[[Category: Humm A]]
-[[Category: Steinbacher, S.]]
+[[Category: Steinbacher S]]
-[[Category: ARG]]
-[[Category: catalytic triad]]
-[[Category: creatine biosynthesis]]
-[[Category: fivefold pseudosymmetry]]
-[[Category: novel fold]]
-[[Category: reaction mechanism]]
-[[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:45:08 2008''

4jdw

From Proteopedia

Current revision

CRYSTAL STRUCTURE AND MECHANISM OF L-ARGININE: GLYCINE AMIDINOTRANSFERASE: A MITOCHONDRIAL ENZYME INVOLVED IN CREATINE BIOSYNTHESIS

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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