6h60

pseudo-atomic structural model of the E3BP component of the human pyruvate dehydrogenase multienzyme complexpseudo-atomic structural model of the E3BP component of the human pyruvate dehydrogenase multienzyme complex

6h60, resolution 6.00Å

Structural highlights

6h60 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.
Gene:	PDHX, PDX1 (HUMAN)
Experimental data:	Check
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ODPX_HUMAN] Defects in PDHX are the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:245349].^[1]

Function

[ODPX_HUMAN] Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.

Publication Abstract from PubMed

The pseudo-atomic structural model of human pyruvate dehydrogenase complex (PDHc) core composed of full-length E2 and E3BP components, calculated from our cryoelectron microscopy-derived density maps at 6-A resolution, is similar to those of prokaryotic E2 structures. The spatial organization of human PDHc components as evidenced by negative-staining electron microscopy and native mass spectrometry is not homogeneous, and entails the unanticipated formation of local clusters of E1:E2 and E3BP:E3 complexes. Such uneven, clustered organization translates into specific duties for E1-E2 clusters (oxidative decarboxylation and acetyl transfer) and E3BP-E3 clusters (regeneration of reduced lipoamide) corresponding to half-reactions of the PDHc catalytic cycle. The addition of substrate coenzyme A modulates the conformational landscape of PDHc, in particular of the lipoyl domains, extending the postulated multiple random coupling mechanism. The conformational and associated chemical landscapes of PDHc are thus not determined entirely stochastically, but are restrained and channeled through an asymmetric architecture and further modulated by substrate binding.

Structural and Functional Analyses of the Human PDH Complex Suggest a "Division-of-Labor" Mechanism by Local E1 and E3 Clusters.,Prajapati S, Haselbach D, Wittig S, Patel MS, Chari A, Schmidt C, Stark H, Tittmann K Structure. 2019 Apr 26. pii: S0969-2126(19)30131-5. doi:, 10.1016/j.str.2019.04.009. PMID:31130485^[2]

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

References

↑ Aral B, Benelli C, Ait-Ghezala G, Amessou M, Fouque F, Maunoury C, Creau N, Kamoun P, Marsac C. Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis. Am J Hum Genet. 1997 Dec;61(6):1318-26. PMID:9399911 doi:S0002-9297(07)60233-X
↑ Prajapati S, Haselbach D, Wittig S, Patel MS, Chari A, Schmidt C, Stark H, Tittmann K. Structural and Functional Analyses of the Human PDH Complex Suggest a "Division-of-Labor" Mechanism by Local E1 and E3 Clusters. Structure. 2019 Apr 26. pii: S0969-2126(19)30131-5. doi:, 10.1016/j.str.2019.04.009. PMID:31130485 doi:http://dx.doi.org/10.1016/j.str.2019.04.009

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

OCA

[1] Aral B, Benelli C, Ait-Ghezala G, Amessou M, Fouque F, Maunoury C, Creau N, Kamoun P, Marsac C. Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis. Am J Hum Genet. 1997 Dec;61(6):1318-26. PMID:9399911 doi:S0002-9297(07)60233-X

[2] Prajapati S, Haselbach D, Wittig S, Patel MS, Chari A, Schmidt C, Stark H, Tittmann K. Structural and Functional Analyses of the Human PDH Complex Suggest a "Division-of-Labor" Mechanism by Local E1 and E3 Clusters. Structure. 2019 Apr 26. pii: S0969-2126(19)30131-5. doi:, 10.1016/j.str.2019.04.009. PMID:31130485 doi:http://dx.doi.org/10.1016/j.str.2019.04.009

[1]

[2]