Structure analysis

Cryo-EM structure of human gamma-secretase in complex with MK-0752

Electron Microscopy
2.7Å resolution
Source organism: Homo sapiens
Assembly composition:
hetero tetramer (preferred)
Entry contents: 4 distinct polypeptide molecules

Assemblies

Assembly 1 (preferred)
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Multimeric state: hetero tetramer
Accessible surface area: 59801.57 Å2
Buried surface area: 19627.6 Å2
Dissociation area: 1,644.11 Å2
Dissociation energy (ΔGdiss): 19.15 kcal/mol
Dissociation entropy (TΔSdiss): 12.75 kcal/mol
Symmetry number: 1
PDBe Complex ID: PDB-CPX-156020

Macromolecules

Chain: B
Length: 467 amino acids
Theoretical weight: 52.71 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49768 (Residues: 1-467; Coverage: 100%)
Gene names: AD3, PS1, PSEN1, PSNL1
Pfam: Presenilin
PDBe-KB: UniProt Coverage View: P49768  
146750100150200250300350400450
 
200400MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
UniProt
P49768
PRO_0000025591
PRO_0000025592
PRO_0000236055
Chains
Secondary structure
Flexibility predictions
Ligand binding sites
Interaction interfaces
Sequence conservation
Variants

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Chain: A
Length: 701 amino acids
Theoretical weight: 77.62 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q92542 (Residues: 1-701; Coverage: 99%)
Gene names: KIAA0253, NCSTN, UNQ1874/PRO4317
Pfam:
PDBe-KB: UniProt Coverage View: Q92542  
170150100150200250300350400450500550600650700
 
200400600MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAP
UniProt
Q92542
Chains
Secondary structure
Ligand binding sites
Interaction interfaces
Sequence conservation
Variants

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Chain: C
Length: 265 amino acids
Theoretical weight: 29.02 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q96BI3 (Residues: 1-265; Coverage: 100%)
Gene names: APH1A, CGI-78, PSF, UNQ579/PRO1141
Pfam: Aph-1 protein
PDBe-KB: UniProt Coverage View: Q96BI3  
126520406080100120140160180200220240260
 
100200MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCRRQEDSRVMVYSALRIPPED
UniProt
Q96BI3
Chains
Secondary structure
Ligand binding sites
Interaction interfaces
Sequence conservation
Variants

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Chain: D
Length: 101 amino acids
Theoretical weight: 12.04 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q9NZ42 (Residues: 1-101; Coverage: 100%)
Gene names: MDS033, PEN2, PSENEN
Pfam: Presenilin enhancer-2 subunit of gamma secretase
PDBe-KB: UniProt Coverage View: Q9NZ42  
1101102030405060708090100
 
50100MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
UniProt
Q9NZ42
Chains
Secondary structure
Interaction interfaces
Sequence conservation
Variants

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