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2ydm

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Revision as of 12:45, 22 July 2020

Structural characterization of angiotensin-I converting enzyme in complex with a selenium analogue of captopril

Structural highlights

2ydm 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:	2iul, 2iux, 1uze, 2c6f, 1uzf, 1o8a, 2xyd, 2xy9, 2c6n, 1o86
Activity:	Peptidyl-dipeptidase A, with EC number 3.4.15.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ACE_HUMAN] Genetic variations in ACE may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.^[1] Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).^[2] Genetic variations in ACE are associated with susceptibility to microvascular complications of diabetes type 3 (MVCD3) [MIM:612624]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in ACE are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:614519]. A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.^[3]

Function

[ACE_HUMAN] Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.

Publication Abstract from PubMed

Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 A resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity. Database Structural data for the two SeCap complexes with ACE and AnCE have been deposited with the RCSB Protein Data Bank under the codes 2YDM and 3ZQZ, respectively.

Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril.,Akif M, Masuyer G, Schwager SL, Bhuyan BJ, Mugesh G, Isaac RE, Sturrock ED, Acharya KR FEBS J. 2011 Aug 2. doi: 10.1111/j.1742-4658.2011.08276.x. PMID:21810173^[4]

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

References

↑ Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004 Nov;61(11):1652-61. PMID:15534175 doi:61/11/1652
↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
↑ Slowik A, Turaj W, Dziedzic T, Haefele A, Pera J, Malecki MT, Glodzik-Sobanska L, Szermer P, Figlewicz DA, Szczudlik A. DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. Neurology. 2004 Jul 27;63(2):359-61. PMID:15277638
↑ Akif M, Masuyer G, Schwager SL, Bhuyan BJ, Mugesh G, Isaac RE, Sturrock ED, Acharya KR. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril. FEBS J. 2011 Aug 2. doi: 10.1111/j.1742-4658.2011.08276.x. PMID:21810173 doi:10.1111/j.1742-4658.2011.08276.x

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Structural characterization of angiotensin-I converting enzyme in complex with a selenium analogue of captopril==
-<StructureSection load='2ydm' size='340' side='right' caption='[[2ydm]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
+<StructureSection load='2ydm' size='340' side='right'caption='[[2ydm]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ydm]] 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=2YDM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YDM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ydm]] 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=2YDM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2YDM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SLC:SELENO-CAPTOPRIL'>SLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SLC:SELENO-CAPTOPRIL'>SLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2iul|2iul]], [[2iux|2iux]], [[1uze|1uze]], [[2c6f|2c6f]], [[1uzf|1uzf]], [[1o8a|1o8a]], [[2xyd|2xyd]], [[2xy9|2xy9]], [[2c6n|2c6n]], [[1o86|1o86]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidyl-dipeptidase_A Peptidyl-dipeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.15.1 3.4.15.1] </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=2ydm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ydm OCA], [http://pdbe.org/2ydm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ydm RCSB], [http://www.ebi.ac.uk/pdbsum/2ydm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ydm ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2ydm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ydm OCA], [http://pdbe.org/2ydm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ydm RCSB], [http://www.ebi.ac.uk/pdbsum/2ydm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ydm ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 24: @@
 ==See Also==
-*[[Angiotensin-Converting Enzyme|Angiotensin-Converting Enzyme]]
+*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
-*[[Carboxypeptidase|Carboxypeptidase]]
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
 == References ==
 <references/>
@@ Line 31: / Line 31: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Peptidyl-dipeptidase A]]
 [[Category: Acharya, K R]]

2ydm

From Proteopedia

Revision as of 12:45, 22 July 2020

Structural characterization of angiotensin-I converting enzyme in complex with a selenium analogue of captopril

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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