Database accession: MF7000931
Name: ChsB1
PDB ID: 7lg9
Experimental method: X-ray (2.03 Å)
Assembly: Homodimer
Source organism: Mycobacterium tuberculosis
Primary publication of the structure:
Yuan T, Werman JM, Yin X, Yang M, Garcia-Diaz M, Sampson NS
Enzymatic β-Oxidation of the Cholesterol Side Chain in Bifurcates Stereospecifically at Hydration of 3-Oxo-cholest-4,22-dien-24-oyl-CoA.
(2021) ACS Infect Dis 7: 1739-1751
PMID: 33826843
Abstract:
The unique ability of Mycobacterium tuberculosis (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, we identify and characterize two genes from the Cho-region (genomic locus responsible for cholesterol catabolism) of the Mtb genome, chsH3 (Rv3538) and chsB1 (Rv3502c). Their protein products catalyze two sequential stereospecific hydration and dehydrogenation steps in the β-oxidation of the cholesterol side chain. ChsH3 favors the 22S hydration of 3-oxo-cholest-4,22-dien-24-oyl-CoA in contrast to the previously reported EchA19 (Rv3516), which catalyzes formation of the (22R)-hydroxy-3-oxo-cholest-4-en-24-oyl-CoA from the same enoyl-CoA substrate. ChsB1 is stereospecific and catalyzes dehydrogenation of the ChsH3 product but not the EchA19 product. The X-ray crystallographic structure of the ChsB1 apo-protein was determined at a resolution of 2.03 Å, and the holo-enzyme with bound NAD+ cofactor was determined at a resolution of 2.21 Å. The homodimeric structure is representative of a classical NAD+-utilizing short-chain type alcohol dehydrogenase/reductase, including a Rossmann-fold motif, but exhibits a unique substrate binding site architecture that is of greater length and width than its homologous counterparts, likely to accommodate the bulky steroid substrate. Intriguingly, Mtb utilizes hydratases from the MaoC-like family in sterol side-chain catabolism in contrast to fatty acid β-oxidation in other species that utilize the evolutionarily distinct crotonase family of hydratases.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
oxidoreductase activity oxidoreductase activity
Biological process:
cholesterol catabolic process cholesterol catabolic process
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Hydroxyacyl-CoA dehydrogenase ChsB1
Source organism: Mycobacterium tuberculosis
Length: 317 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKLTESNRSPRTTNTTDLSGKVAVVTGAAAGLGRAEALGLARLGATVVVNDVASALDASDVVDEIGAAAADAGAKAVAVAGDISQRATADELLASAVGLGGLDIVVNNAGITRDRMLFNMSDEEWDAVIAVHLRGHFLLTRNAAAYWRDKAKDAEGGSVFGRLVNTSSEAGLVGPVGQANYAAAKAGITALTLSAARALGRYGVCANVICPRARTAMTADVFGAAPDVEAGQIDPLSPQHVVSLVQFLASPAAAEVNGQVFIVYGPQVTLVSPPHMERRFSADGTSWDPTELTATLRDYFAGRDPEQSFSATDLMRQ
UniProtKB AC: O53547 (positions: 15-304)
Coverage: 91%
Name: Hydroxyacyl-CoA dehydrogenase ChsB1
Source organism: Mycobacterium tuberculosis
Length: 317 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKLTESNRSPRTTNTTDLSGKVAVVTGAAAGLGRAEALGLARLGATVVVNDVASALDASDVVDEIGAAAADAGAKAVAVAGDISQRATADELLASAVGLGGLDIVVNNAGITRDRMLFNMSDEEWDAVIAVHLRGHFLLTRNAAAYWRDKAKDAEGGSVFGRLVNTSSEAGLVGPVGQANYAAAKAGITALTLSAARALGRYGVCANVICPRARTAMTADVFGAAPDVEAGQIDPLSPQHVVSLVQFLASPAAAEVNGQVFIVYGPQVTLVSPPHMERRFSADGTSWDPTELTATLRDYFAGRDPEQSFSATDLMRQ
UniProtKB AC: O53547 (positions: 16-304)
Coverage: 91%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Short chain dehydrogenase
Evidence level: Insufficient evidence (candidate)
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
There is a knot-like interface between individual monomers. The structure looks like a domain-swapped Rossmann fold unit. The two largest helices, α7 and α9, which are parallel, form the majority of the dimer interface. Analytical ultracentrifugation sedimentation velocity analysis suggests homodimeric structure (PMID:33826843).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
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