2fy3

From Proteopedia

(Difference between revisions)

Revision as of 17:59, 10 September 2015

Structures of ligand bound human choline acetyltransferase provides insight into regulation of acetylcholine synthesis

Structural highlights

2fy3 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1fy2, 1fy4, 1fy5
Gene:	CHAT (HUMAN)
Activity:	Choline O-acetyltransferase, with EC number 2.3.1.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[CLAT_HUMAN] Defects in CHAT are the cause of congenital myasthenic syndrome with episodic apnea (CMSEA) [MIM:254210]; formerly known as familial infantile myasthenia gravis 2 (FIMG2). CMSEA is an autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.^[1] ^[2]

Function

[CLAT_HUMAN] Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.

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

Choline acetyltransferase (ChAT) catalyzes the synthesis of the neurotransmitter acetylcholine from choline and acetyl-CoA, and its presence is a defining feature of cholinergic neurons. We report the structure of human ChAT to a resolution of 2.2 A along with structures for binary complexes of ChAT with choline, CoA, and a nonhydrolyzable acetyl-CoA analogue, S-(2-oxopropyl)-CoA. The ChAT-choline complex shows which features of choline are important for binding and explains how modifications of the choline trimethylammonium group can be tolerated by the enzyme. A detailed model of the ternary Michaelis complex fully supports the direct transfer of the acetyl group from acetyl-CoA to choline through a mechanism similar to that seen in the serine hydrolases for the formation of an acyl-enzyme intermediate. Domain movements accompany CoA binding, and a surface loop, which is disordered in the unliganded enzyme, becomes localized and binds directly to the phosphates of CoA, stabilizing the complex. Interactions between this surface loop and CoA may function to lower the KM for CoA and could be important for phosphorylation-dependent regulation of ChAT activity.

Substrate binding and catalytic mechanism of human choline acetyltransferase.,Kim AR, Rylett RJ, Shilton BH Biochemistry. 2006 Dec 12;45(49):14621-31. PMID:17144655^[3]

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

References

↑ Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2017-22. PMID:11172068 doi:10.1073/pnas.98.4.2017
↑ Kraner S, Laufenberg I, Strassburg HM, Sieb JP, Steinlein OK. Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. Arch Neurol. 2003 May;60(5):761-3. PMID:12756141 doi:10.1001/archneur.60.5.761
↑ Kim AR, Rylett RJ, Shilton BH. Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry. 2006 Dec 12;45(49):14621-31. PMID:17144655 doi:10.1021/bi061536l

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2fy3"

@@ Line 2: / Line 2: @@
 <StructureSection load='2fy3' size='340' side='right' caption='[[2fy3]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2fy3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FY3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2fy3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FY3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fy2|1fy2]], [[1fy4|1fy4]], [[1fy5|1fy5]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Choline_O-acetyltransferase Choline O-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.6 2.3.1.6] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fy3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fy3 RCSB], [http://www.ebi.ac.uk/pdbsum/2fy3 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fy3 OCA], [http://pdbe.org/2fy3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fy3 RCSB], [http://www.ebi.ac.uk/pdbsum/2fy3 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2fy3" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 39: / Line 40: @@
 </StructureSection>
 [[Category: Choline O-acetyltransferase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Kim, A R]]
 [[Category: Rylett, R J]]

2fy3

From Proteopedia

Revision as of 17:59, 10 September 2015

Structures of ligand bound human choline acetyltransferase provides insight into regulation of acetylcholine synthesis

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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