Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

2CW6

Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000287	molecular_function	magnesium ion binding
A	0003824	molecular_function	catalytic activity
A	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
A	0005198	molecular_function	structural molecule activity
A	0005739	cellular_component	mitochondrion
A	0005759	cellular_component	mitochondrial matrix
A	0005777	cellular_component	peroxisome
A	0005782	cellular_component	peroxisomal matrix
A	0005829	cellular_component	cytosol
A	0006552	biological_process	L-leucine catabolic process
A	0006629	biological_process	lipid metabolic process
A	0007005	biological_process	mitochondrion organization
A	0016829	molecular_function	lyase activity
A	0016833	molecular_function	oxo-acid-lyase activity
A	0030145	molecular_function	manganese ion binding
A	0032991	cellular_component	protein-containing complex
A	0046872	molecular_function	metal ion binding
A	0046951	biological_process	ketone body biosynthetic process
B	0000287	molecular_function	magnesium ion binding
B	0003824	molecular_function	catalytic activity
B	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
B	0005198	molecular_function	structural molecule activity
B	0005739	cellular_component	mitochondrion
B	0005759	cellular_component	mitochondrial matrix
B	0005777	cellular_component	peroxisome
B	0005782	cellular_component	peroxisomal matrix
B	0005829	cellular_component	cytosol
B	0006552	biological_process	L-leucine catabolic process
B	0006629	biological_process	lipid metabolic process
B	0007005	biological_process	mitochondrion organization
B	0016829	molecular_function	lyase activity
B	0016833	molecular_function	oxo-acid-lyase activity
B	0030145	molecular_function	manganese ion binding
B	0032991	cellular_component	protein-containing complex
B	0046872	molecular_function	metal ion binding
B	0046951	biological_process	ketone body biosynthetic process
C	0000287	molecular_function	magnesium ion binding
C	0003824	molecular_function	catalytic activity
C	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
C	0005198	molecular_function	structural molecule activity
C	0005739	cellular_component	mitochondrion
C	0005759	cellular_component	mitochondrial matrix
C	0005777	cellular_component	peroxisome
C	0005782	cellular_component	peroxisomal matrix
C	0005829	cellular_component	cytosol
C	0006552	biological_process	L-leucine catabolic process
C	0006629	biological_process	lipid metabolic process
C	0007005	biological_process	mitochondrion organization
C	0016829	molecular_function	lyase activity
C	0016833	molecular_function	oxo-acid-lyase activity
C	0030145	molecular_function	manganese ion binding
C	0032991	cellular_component	protein-containing complex
C	0046872	molecular_function	metal ion binding
C	0046951	biological_process	ketone body biosynthetic process
D	0000287	molecular_function	magnesium ion binding
D	0003824	molecular_function	catalytic activity
D	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
D	0005198	molecular_function	structural molecule activity
D	0005739	cellular_component	mitochondrion
D	0005759	cellular_component	mitochondrial matrix
D	0005777	cellular_component	peroxisome
D	0005782	cellular_component	peroxisomal matrix
D	0005829	cellular_component	cytosol
D	0006552	biological_process	L-leucine catabolic process
D	0006629	biological_process	lipid metabolic process
D	0007005	biological_process	mitochondrion organization
D	0016829	molecular_function	lyase activity
D	0016833	molecular_function	oxo-acid-lyase activity
D	0030145	molecular_function	manganese ion binding
D	0032991	cellular_component	protein-containing complex
D	0046872	molecular_function	metal ion binding
D	0046951	biological_process	ketone body biosynthetic process
E	0000287	molecular_function	magnesium ion binding
E	0003824	molecular_function	catalytic activity
E	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
E	0005198	molecular_function	structural molecule activity
E	0005739	cellular_component	mitochondrion
E	0005759	cellular_component	mitochondrial matrix
E	0005777	cellular_component	peroxisome
E	0005782	cellular_component	peroxisomal matrix
E	0005829	cellular_component	cytosol
E	0006552	biological_process	L-leucine catabolic process
E	0006629	biological_process	lipid metabolic process
E	0007005	biological_process	mitochondrion organization
E	0016829	molecular_function	lyase activity
E	0016833	molecular_function	oxo-acid-lyase activity
E	0030145	molecular_function	manganese ion binding
E	0032991	cellular_component	protein-containing complex
E	0046872	molecular_function	metal ion binding
E	0046951	biological_process	ketone body biosynthetic process
F	0000287	molecular_function	magnesium ion binding
F	0003824	molecular_function	catalytic activity
F	0004419	molecular_function	hydroxymethylglutaryl-CoA lyase activity
F	0005198	molecular_function	structural molecule activity
F	0005739	cellular_component	mitochondrion
F	0005759	cellular_component	mitochondrial matrix
F	0005777	cellular_component	peroxisome
F	0005782	cellular_component	peroxisomal matrix
F	0005829	cellular_component	cytosol
F	0006552	biological_process	L-leucine catabolic process
F	0006629	biological_process	lipid metabolic process
F	0007005	biological_process	mitochondrion organization
F	0016829	molecular_function	lyase activity
F	0016833	molecular_function	oxo-acid-lyase activity
F	0030145	molecular_function	manganese ion binding
F	0032991	cellular_component	protein-containing complex
F	0046872	molecular_function	metal ion binding
F	0046951	biological_process	ketone body biosynthetic process

Functional Information from PDB Data

site_id	AC1
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG A 401

Chain	Residue
A	ASP42
A	HIS233
A	HIS235
A	ASN275
A	HOH763
A	HOH920

site_id	AC2
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG E 402

Chain	Residue
E	ASN275
E	HOH860
E	ASP42
E	HIS233
E	HIS235

site_id	AC3
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG C 403

Chain	Residue
C	ASP42
C	HIS233
C	HIS235
C	ASN275
C	HOH898

site_id	AC4
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG B 404

Chain	Residue
B	ASP42
B	HIS233
B	HIS235
B	ASN275
B	HOH712
B	HOH938

site_id	AC5
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG D 405

Chain	Residue
D	ASP42
D	HIS233
D	HIS235
D	ASN275
D	HOH777

site_id	AC6
Number of Residues	4
Details	BINDING SITE FOR RESIDUE MG F 406

Chain	Residue
F	ASP42
F	HIS233
F	HIS235
F	ASN275

site_id	AC7
Number of Residues	5
Details	BINDING SITE FOR RESIDUE 3HG A 399

Chain	Residue
A	ARG41
A	GLN45
A	LEU106
A	PHE127
A	HOH530

Functional Information from PROSITE/UniProt

site_id	PS01062
Number of Residues	10
Details	HMG_COA_LYASE Hydroxymethylglutaryl-coenzyme A lyase active site. SVAGLGGCPY

Chain	Residue	Details
A	SER259-TYR268

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	6
Details	ACT_SITE: ACT_SITE => ECO:0000255\|PROSITE-ProRule:PRU10115

Chain	Residue	Details
A	CYS266
B	CYS266
C	CYS266
D	CYS266
E	CYS266
F	CYS266

site_id	SWS_FT_FI2
Number of Residues	30
Details	BINDING:

Chain	Residue	Details
A	ARG41
B	ASN275
C	ARG41
C	ASP42
C	HIS233
C	HIS235
C	ASN275
D	ARG41
D	ASP42
D	HIS233
D	HIS235
A	ASP42
D	ASN275
E	ARG41
E	ASP42
E	HIS233
E	HIS235
E	ASN275
F	ARG41
F	ASP42
F	HIS233
F	HIS235
A	HIS233
F	ASN275
A	HIS235
A	ASN275
B	ARG41
B	ASP42
B	HIS233
B	HIS235

site_id	SWS_FT_FI3
Number of Residues	18
Details	MOD_RES: N6-succinyllysine; alternate => ECO:0000250\|UniProtKB:P38060

Chain	Residue	Details
A	LYS48
D	LYS48
D	LYS137
D	LYS179
E	LYS48
E	LYS137
E	LYS179
F	LYS48
F	LYS137
F	LYS179
A	LYS137
A	LYS179
B	LYS48
B	LYS137
B	LYS179
C	LYS48
C	LYS137
C	LYS179

site_id	SWS_FT_FI4
Number of Residues	12
Details	MOD_RES: N6-acetyllysine => ECO:0000250\|UniProtKB:P38060

Chain	Residue	Details
A	LYS111
E	LYS324
F	LYS111
F	LYS324
A	LYS324
B	LYS111
B	LYS324
C	LYS111
C	LYS324
D	LYS111
D	LYS324
E	LYS111

		Sequence (fasta)
		PDBx/mmCIF
		PDBML format (no-atom)
		PDB format (full)
		Validation report (PDF)
		EDMap 2fo-fc (MTZ)