3exh: Difference between revisions

Revision as of 22:47, 20 October 2021

Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complexCrystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex

Structural highlights

3exh is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:
Related:	3exe, 3exf, 3exg, 3exi
Gene:	PDHA1, PHE1A (HUMAN), PDHB, PHE1B (HUMAN)
Activity:	Pyruvate dehydrogenase (acetyl-transferring), with EC number 1.2.4.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ODPA_HUMAN] Defects in PDHA1 are a cause of pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:312170]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:308930]. X-LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes.^[15] ^[16] ^[17] ^[18] ^[19] [ODPB_HUMAN] Defects in PDHB are the cause of pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.^[20]

Function

[ODPA_HUMAN] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.^[21] ^[22] [ODPB_HUMAN] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.^[23] ^[24]

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

We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-alpha (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-alpha prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-alpha, which nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.

Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops.,Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061^[25]

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

References

↑ Ito M, Huq AH, Naito E, Saijo T, Takeda E, Kuroda Y. Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein. J Inherit Metab Dis. 1992;15(6):848-56. PMID:1338114
↑ Hansen LL, Brown GK, Kirby DM, Dahl HH. Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. J Inherit Metab Dis. 1991;14(2):140-51. PMID:1909401
↑ De Meirleir L, Lissens W, Vamos E, Liebaers I. Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit. Hum Genet. 1992 Mar;88(6):649-52. PMID:1551669
↑ Dahl HH, Hansen LL, Brown RM, Danks DM, Rogers JG, Brown GK. X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. J Inherit Metab Dis. 1992;15(6):835-47. PMID:1293379
↑ Chun K, MacKay N, Petrova-Benedict R, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. Hum Mol Genet. 1993 Apr;2(4):449-54. PMID:8504306
↑ Matthews PM, Brown RM, Otero LJ, Marchington DR, LeGris M, Howes R, Meadows LS, Shevell M, Scriver CR, Brown GK. Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. Brain. 1994 Jun;117 ( Pt 3):435-43. PMID:8032855
↑ Hansen LL, Horn N, Dahl HH, Kruse TA. Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in the PDH E1 alpha subunit. Hum Mol Genet. 1994 Jun;3(6):1021-2. PMID:7545958
↑ Awata H, Endo F, Tanoue A, Kitano A, Matsuda I. Characterization of a point mutation in the pyruvate dehydrogenase E1 alpha gene from two boys with primary lactic acidaemia. J Inherit Metab Dis. 1994;17(2):189-95. PMID:7967473
↑ Chun K, MacKay N, Petrova-Benedict R, Federico A, Fois A, Cole DE, Robertson E, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex. Am J Hum Genet. 1995 Mar;56(3):558-69. PMID:7887409
↑ Takakubo F, Cartwright P, Hoogenraad N, Thorburn DR, Collins F, Lithgow T, Dahl HH. An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. Am J Hum Genet. 1995 Oct;57(4):772-80. PMID:7573035
↑ Hemalatha SG, Kerr DS, Wexler ID, Lusk MM, Kaung M, Du Y, Kolli M, Schelper RL, Patel MS. Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L) within the thiamine pyrophosphate binding loop of the E1 alpha subunit. Hum Mol Genet. 1995 Feb;4(2):315-8. PMID:7757088
↑ Lissens W, De Meirleir L, Seneca S, Benelli C, Marsac C, Poll-The BT, Briones P, Ruitenbeek W, van Diggelen O, Chaigne D, Ramaekers V, Liebaers I. Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency. Hum Mutat. 1996;7(1):46-51. PMID:8664900 doi:<46::AID-HUMU6>3.0.CO;2-N 10.1002/(SICI)1098-1004(1996)7:1<46::AID-HUMU6>3.0.CO;2-N
↑ Tripatara A, Kerr DS, Lusk MM, Kolli M, Tan J, Patel MS. Three new mutations of the pyruvate dehydrogenase alpha subunit: a point mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift (K358SVS-->TVDQS). Hum Mutat. 1996;8(2):180-2. PMID:8844217 doi:<180::AID-HUMU11>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1996)8:2<180::AID-HUMU11>3.0.CO;2-Z
↑ Otero LJ, Brown RM, Brown GK. Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity. Hum Mutat. 1998;12(2):114-21. PMID:9671272 doi:<114::AID-HUMU6>3.0.CO;2-# 10.1002/(SICI)1098-1004(1998)12:2<114::AID-HUMU6>3.0.CO;2-#
↑ Hansen LL, Brown GK, Kirby DM, Dahl HH. Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. J Inherit Metab Dis. 1991;14(2):140-51. PMID:1909401
↑ Chun K, MacKay N, Petrova-Benedict R, Federico A, Fois A, Cole DE, Robertson E, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex. Am J Hum Genet. 1995 Mar;56(3):558-69. PMID:7887409
↑ Matthews PM, Marchington DR, Squier M, Land J, Brown RM, Brown GK. Molecular genetic characterization of an X-linked form of Leigh's syndrome. Ann Neurol. 1993 Jun;33(6):652-5. PMID:8498846 doi:http://dx.doi.org/10.1002/ana.410330616
↑ Dahl HH, Brown GK. Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. Hum Mutat. 1994;3(2):152-5. PMID:8199595 doi:http://dx.doi.org/10.1002/humu.1380030210
↑ Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Osaka H, Kimura S, Kuroda Y. Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. J Inherit Metab Dis. 1997 Aug;20(4):539-48. PMID:9266390
↑ Brown RM, Head RA, Boubriak II, Leonard JV, Thomas NH, Brown GK. Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. Hum Genet. 2004 Jul;115(2):123-7. Epub 2004 May 11. PMID:15138885 doi:10.1007/s00439-004-1124-8
↑ Korotchkina LG, Patel MS. Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. J Biol Chem. 1995 Jun 16;270(24):14297-304. PMID:7782287
↑ Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010
↑ Seifert F, Ciszak E, Korotchkina L, Golbik R, Spinka M, Dominiak P, Sidhu S, Brauer J, Patel MS, Tittmann K. Phosphorylation of serine 264 impedes active site accessibility in the E1 component of the human pyruvate dehydrogenase multienzyme complex. Biochemistry. 2007 May 29;46(21):6277-87. Epub 2007 May 3. PMID:17474719 doi:http://dx.doi.org/10.1021/bi700083z
↑ Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010
↑ Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Ito M, Huq AH, Naito E, Saijo T, Takeda E, Kuroda Y. Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein. J Inherit Metab Dis. 1992;15(6):848-56. PMID:1338114

[2] Hansen LL, Brown GK, Kirby DM, Dahl HH. Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. J Inherit Metab Dis. 1991;14(2):140-51. PMID:1909401

[3] De Meirleir L, Lissens W, Vamos E, Liebaers I. Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit. Hum Genet. 1992 Mar;88(6):649-52. PMID:1551669

[4] Dahl HH, Hansen LL, Brown RM, Danks DM, Rogers JG, Brown GK. X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. J Inherit Metab Dis. 1992;15(6):835-47. PMID:1293379

[5] Chun K, MacKay N, Petrova-Benedict R, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. Hum Mol Genet. 1993 Apr;2(4):449-54. PMID:8504306

[6] Matthews PM, Brown RM, Otero LJ, Marchington DR, LeGris M, Howes R, Meadows LS, Shevell M, Scriver CR, Brown GK. Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. Brain. 1994 Jun;117 ( Pt 3):435-43. PMID:8032855

[7] Hansen LL, Horn N, Dahl HH, Kruse TA. Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in the PDH E1 alpha subunit. Hum Mol Genet. 1994 Jun;3(6):1021-2. PMID:7545958

[8] Awata H, Endo F, Tanoue A, Kitano A, Matsuda I. Characterization of a point mutation in the pyruvate dehydrogenase E1 alpha gene from two boys with primary lactic acidaemia. J Inherit Metab Dis. 1994;17(2):189-95. PMID:7967473

[9] Chun K, MacKay N, Petrova-Benedict R, Federico A, Fois A, Cole DE, Robertson E, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex. Am J Hum Genet. 1995 Mar;56(3):558-69. PMID:7887409

[10] Takakubo F, Cartwright P, Hoogenraad N, Thorburn DR, Collins F, Lithgow T, Dahl HH. An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. Am J Hum Genet. 1995 Oct;57(4):772-80. PMID:7573035

[11] Hemalatha SG, Kerr DS, Wexler ID, Lusk MM, Kaung M, Du Y, Kolli M, Schelper RL, Patel MS. Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L) within the thiamine pyrophosphate binding loop of the E1 alpha subunit. Hum Mol Genet. 1995 Feb;4(2):315-8. PMID:7757088

[12] Lissens W, De Meirleir L, Seneca S, Benelli C, Marsac C, Poll-The BT, Briones P, Ruitenbeek W, van Diggelen O, Chaigne D, Ramaekers V, Liebaers I. Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency. Hum Mutat. 1996;7(1):46-51. PMID:8664900 doi:<46::AID-HUMU6>3.0.CO;2-N 10.1002/(SICI)1098-1004(1996)7:1<46::AID-HUMU6>3.0.CO;2-N

[13] Tripatara A, Kerr DS, Lusk MM, Kolli M, Tan J, Patel MS. Three new mutations of the pyruvate dehydrogenase alpha subunit: a point mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift (K358SVS-->TVDQS). Hum Mutat. 1996;8(2):180-2. PMID:8844217 doi:<180::AID-HUMU11>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1996)8:2<180::AID-HUMU11>3.0.CO;2-Z

[14] Otero LJ, Brown RM, Brown GK. Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity. Hum Mutat. 1998;12(2):114-21. PMID:9671272 doi:<114::AID-HUMU6>3.0.CO;2-# 10.1002/(SICI)1098-1004(1998)12:2<114::AID-HUMU6>3.0.CO;2-#

[15] Hansen LL, Brown GK, Kirby DM, Dahl HH. Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. J Inherit Metab Dis. 1991;14(2):140-51. PMID:1909401

[16] Chun K, MacKay N, Petrova-Benedict R, Federico A, Fois A, Cole DE, Robertson E, Robinson BH. Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex. Am J Hum Genet. 1995 Mar;56(3):558-69. PMID:7887409

[17] Matthews PM, Marchington DR, Squier M, Land J, Brown RM, Brown GK. Molecular genetic characterization of an X-linked form of Leigh's syndrome. Ann Neurol. 1993 Jun;33(6):652-5. PMID:8498846 doi:http://dx.doi.org/10.1002/ana.410330616

[18] Dahl HH, Brown GK. Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. Hum Mutat. 1994;3(2):152-5. PMID:8199595 doi:http://dx.doi.org/10.1002/humu.1380030210

[19] Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Osaka H, Kimura S, Kuroda Y. Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. J Inherit Metab Dis. 1997 Aug;20(4):539-48. PMID:9266390

[20] Brown RM, Head RA, Boubriak II, Leonard JV, Thomas NH, Brown GK. Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. Hum Genet. 2004 Jul;115(2):123-7. Epub 2004 May 11. PMID:15138885 doi:10.1007/s00439-004-1124-8

[21] Korotchkina LG, Patel MS. Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. J Biol Chem. 1995 Jun 16;270(24):14297-304. PMID:7782287

[22] Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010

[23] Seifert F, Ciszak E, Korotchkina L, Golbik R, Spinka M, Dominiak P, Sidhu S, Brauer J, Patel MS, Tittmann K. Phosphorylation of serine 264 impedes active site accessibility in the E1 component of the human pyruvate dehydrogenase multienzyme complex. Biochemistry. 2007 May 29;46(21):6277-87. Epub 2007 May 3. PMID:17474719 doi:http://dx.doi.org/10.1021/bi700083z

[24] Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010

[25] Kato M, Wynn RM, Chuang JL, Tso SC, Machius M, Li J, Chuang DT. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure. 2008 Dec 10;16(12):1849-59. PMID:19081061 doi:10.1016/j.str.2008.10.010

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@@ Line 1: / Line 1: @@
 ==Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex==
-<StructureSection load='3exh' size='340' side='right' caption='[[3exh]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
+<StructureSection load='3exh' size='340' side='right'caption='[[3exh]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3exh]] is a 8 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=3EXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EXH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3exh]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EXH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3exe|3exe]], [[3exf|3exf]], [[3exg|3exg]], [[3exi|3exi]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3exe|3exe]], [[3exf|3exf]], [[3exg|3exg]], [[3exi|3exi]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDHA1, PHE1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDHB, PHE1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDHA1, PHE1A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDHB, PHE1B ([https://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/Pyruvate_dehydrogenase_(acetyl-transferring) Pyruvate dehydrogenase (acetyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.1 1.2.4.1] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_(acetyl-transferring) Pyruvate dehydrogenase (acetyl-transferring)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.1 1.2.4.1] </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=3exh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3exh OCA], [http://pdbe.org/3exh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3exh RCSB], [http://www.ebi.ac.uk/pdbsum/3exh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3exh ProSAT]</span></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=3exh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3exh OCA], [https://pdbe.org/3exh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3exh RCSB], [https://www.ebi.ac.uk/pdbsum/3exh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3exh ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN]] Defects in PDHA1 are a cause of pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:[http://omim.org/entry/312170 312170]]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.<ref>PMID:1338114</ref> <ref>PMID:1909401</ref> <ref>PMID:1551669</ref> <ref>PMID:1293379</ref> <ref>PMID:8504306</ref> <ref>PMID:8032855</ref> <ref>PMID:7545958</ref> <ref>PMID:7967473</ref> <ref>PMID:7887409</ref> <ref>PMID:7573035</ref> <ref>PMID:7757088</ref> <ref>PMID:8664900</ref> <ref>PMID:8844217</ref> <ref>PMID:9671272</ref>   Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:[http://omim.org/entry/308930 308930]]. X-LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes.<ref>PMID:1909401</ref> <ref>PMID:7887409</ref> <ref>PMID:8498846</ref> <ref>PMID:8199595</ref> <ref>PMID:9266390</ref>  [[http://www.uniprot.org/uniprot/ODPB_HUMAN ODPB_HUMAN]] Defects in PDHB are the cause of pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:[http://omim.org/entry/614111 614111]]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.<ref>PMID:15138885</ref>
+[[https://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN]] Defects in PDHA1 are a cause of pyruvate dehydrogenase E1-alpha deficiency (PDHAD) [MIM:[https://omim.org/entry/312170 312170]]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.<ref>PMID:1338114</ref> <ref>PMID:1909401</ref> <ref>PMID:1551669</ref> <ref>PMID:1293379</ref> <ref>PMID:8504306</ref> <ref>PMID:8032855</ref> <ref>PMID:7545958</ref> <ref>PMID:7967473</ref> <ref>PMID:7887409</ref> <ref>PMID:7573035</ref> <ref>PMID:7757088</ref> <ref>PMID:8664900</ref> <ref>PMID:8844217</ref> <ref>PMID:9671272</ref>   Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:[https://omim.org/entry/308930 308930]]. X-LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes.<ref>PMID:1909401</ref> <ref>PMID:7887409</ref> <ref>PMID:8498846</ref> <ref>PMID:8199595</ref> <ref>PMID:9266390</ref>  [[https://www.uniprot.org/uniprot/ODPB_HUMAN ODPB_HUMAN]] Defects in PDHB are the cause of pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:[https://omim.org/entry/614111 614111]]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.<ref>PMID:15138885</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:7782287</ref> <ref>PMID:19081061</ref>  [[http://www.uniprot.org/uniprot/ODPB_HUMAN ODPB_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:17474719</ref> <ref>PMID:19081061</ref>
+[[https://www.uniprot.org/uniprot/ODPA_HUMAN ODPA_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:7782287</ref> <ref>PMID:19081061</ref>  [[https://www.uniprot.org/uniprot/ODPB_HUMAN ODPB_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.<ref>PMID:17474719</ref> <ref>PMID:19081061</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/ex/3exh_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ex/3exh_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 34: / Line 34: @@
 </div>
 <div class="pdbe-citations 3exh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Pyruvate dehydrogenase 3D structures|Pyruvate dehydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 42: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chuang, D T]]
 [[Category: Chuang, J L]]

3exh: Difference between revisions

Revision as of 22:47, 20 October 2021

Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complexCrystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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3exh: Difference between revisions

Revision as of 22:47, 20 October 2021

Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complexCrystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Search