6O0A

Crystal structure of flavohemoglobin from Malassezia yamatoensis with bound FAD and heme determined by iron SAD phasing

Summary for 6O0A

• Entry DOI: 10.2210/pdb6o0a/pdb
• Descriptor: Flavohemoglobin, FLAVIN-ADENINE DINUCLEOTIDE, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: ssgcid, fad, heme, flavohemoglobin, oxidoreductase, structural genomics, seattle structural genomics center for infectious disease
• Biological source: Malassezia yamatoensis
• Total number of polymer chains: 1
• Total formula weight: 47763.94

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2019-02-15, release date: 2019-03-06, Last modification date: 2024-05-22)

Primary citation

Ianiri, G.,Coelho, M.A.,Ruchti, F.,Sparber, F.,McMahon, T.J.,Fu, C.,Bolejack, M.,Donovan, O.,Smutney, H.,Myler, P.,Dietrich, F.,Fox 3rd, D.,LeibundGut-Landmann, S.,Heitman, J.
HGT in the human and skin commensal Malassezia : A bacterially derived flavohemoglobin is required for NO resistance and host interaction.
Proc.Natl.Acad.Sci.USA, 117:15884-15894, 2020

PubMed Abstract: The skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions. are the most abundant fungal skin inhabitant of warm-blooded animals and have been implicated in skin diseases and systemic disorders, including Crohn's disease and pancreatic cancer. Flavohemoglobin is a key enzyme involved in microbial nitrosative stress resistance and nitric oxide degradation. Comparative genomics and phylogenetic analyses within the genus revealed that flavohemoglobin-encoding genes were acquired through independent horizontal gene transfer events from different donor bacteria that are part of the mammalian microbiome. Through targeted gene deletion and functional complementation in , we demonstrated that bacterially derived flavohemoglobins are cytoplasmic proteins required for nitric oxide detoxification and nitrosative stress resistance under aerobic conditions. RNA-sequencing analysis revealed that endogenous accumulation of nitric oxide resulted in up-regulation of genes involved in stress response and down-regulation of the MalaS7 allergen-encoding genes. Solution of the high-resolution X-ray crystal structure of flavohemoglobin revealed features conserved with both bacterial and fungal flavohemoglobins. In vivo pathogenesis is independent of flavohemoglobin. Lastly, we identified an additional 30 genus- and species-specific horizontal gene transfer candidates that might have contributed to the evolution of this genus as the most common inhabitants of animal skin.

PubMed: 32576698
DOI: 10.1073/pnas.2003473117

Experimental method

X-RAY DIFFRACTION (1.7 Å)