View source for 9uhb


==BCCP-CT Conformation of AMPPNP-bound hPCC==
<StructureSection load='9uhb' size='340' side='right'caption='[[9uhb]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9uhb]] is a 3 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=9UHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UHB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.16&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1VU:PROPIONYL+COENZYME+A'>1VU</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=BTN:BIOTIN'>BTN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9uhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9uhb OCA], [https://pdbe.org/9uhb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9uhb RCSB], [https://www.ebi.ac.uk/pdbsum/9uhb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9uhb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PCCA_HUMAN PCCA_HUMAN] Defects in PCCA are the cause of propionic acidemia type I (PA-1) [MIM:[https://omim.org/entry/606054 606054]. PA-1 is a life-threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein.<ref>PMID:10101253</ref> <ref>PMID:12559849</ref> <ref>PMID:15059621</ref> <ref>PMID:10329019</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PCCA_HUMAN PCCA_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Propionyl-CoA carboxylase (PCC) is a biotin-dependent mitochondrial enzyme responsible for propionyl-CoA catabolism. Deficiencies in human PCC (hPCC) cause propionic acidemia, a severe metabolic disorder driven by toxic metabolite accumulation. Despite its therapeutic relevance, the structural basis of hPCC's catalytic function remains unresolved. Here, we present high-resolution cryo-EM structures of hPCC in four distinct states, unliganded, ADP-, AMPPNP-, and ATP-bound/substrate-bound, capturing the full trajectory of the biotin carboxyl carrier protein (BCCP) domain as it translocates between active sites. Our results reinforce the crucial role of nucleotide-gated B-lid subdomain in synchronizing catalysis through coupling with BCCP movement. Structural and biochemical analysis of 10 disease-associated variants reveals how mutations disrupt key domain interfaces and dynamic motions required for activity. These new insights define the mechanistic principles governing hPCC functions, establish a structural framework for understanding PCC-related disorders, and lay the groundwork for future efforts to engineer functional replacements or modulators for metabolic therapy.

Nanoscale conformational dynamics of human propionyl-CoA carboxylase.,Yan H, Ni F, Wang Q, Ma J Structure. 2025 Nov 5:S0969-2126(25)00396-X. doi: 10.1016/j.str.2025.10.009. PMID:41197621<ref>PMID:41197621</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9uhb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ma JP]]
[[Category: Ni FY]]
[[Category: Wang QH]]
[[Category: Yan HF]]