Literature summary for 2.5.1.61 extracted from

Bung, N.; Roy, A.; Chen, B.; Das, D.; Pradhan, M.; Yasuda, M.; New, M.I.; Desnick, R.J.; Bulusu, G.
Human hydroxymethylbilane synthase Molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP (2018), Proc. Natl. Acad. Sci. USA, 115, E4071-E4080 .

Crystallization (Commentary)

Crystallization (Comment)	Organism
molecular dynamics simulations reveal that the HMBS active-site loop movement and cofactor turn create space for the elongating pyrrole chain. Twenty-seven residues around the active site and water molecules interact to stabilize the large, negatively charged, elongating polypyrrole. Residues R26 and R167 are the strongest candidates for proton transfer to deaminate the incoming porphobilinogen molecules. R167 is a gatekeeper and facilitator of hydroxymethylbilane egress through the space between the enzyme's domains and the active-site loop	Homo sapiens

Crystallization (Comment)

Organism

molecular dynamics simulations reveal that the HMBS active-site loop movement and cofactor turn create space for the elongating pyrrole chain. Twenty-seven residues around the active site and water molecules interact to stabilize the large, negatively charged, elongating polypyrrole. Residues R26 and R167 are the strongest candidates for proton transfer to deaminate the incoming porphobilinogen molecules. R167 is a gatekeeper and facilitator of hydroxymethylbilane egress through the space between the enzyme's domains and the active-site loop

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A31P	0.6% of wild-type activity	Homo sapiens
A31T	0.50% of wild-type activity	Homo sapiens
D99G	3.2% of wild-type activity	Homo sapiens
D99H	3.3% of wild-type activity	Homo sapiens
G218R	0.1% of wild-type activity	Homo sapiens
K98R	0.70% of wild-type activity	Homo sapiens
L170R	0.6% of wild-type activity	Homo sapiens
L170V	72.6% of wild-type activity	Homo sapiens
N169I	6.2% of wild-type activity	Homo sapiens
Q34K	0.2% of wild-type activity	Homo sapiens
Q34R	0.7% of wild-type activity	Homo sapiens
Q356E	95.7% of wild-type activity	Homo sapiens
R149L	0.1% of wild-type activity	Homo sapiens
R149Q	0.5% of wild-type activity	Homo sapiens
R150I	0.02% of wild-type activity	Homo sapiens
R150Q	0.8% of wild-type activity	Homo sapiens
R167Q	1.0% of wild-type activity	Homo sapiens
R167W	2.3% of wild-type activity	Homo sapiens
R173Q	0.4% of wild-type activity	Homo sapiens
R173W	0.7% of wild-type activity	Homo sapiens
R195C	3% of wild-type activity	Homo sapiens
R26C	0.3% of wild-type activity	Homo sapiens
R26H	0.3% of wild-type activity	Homo sapiens
S146C	69.9% of wild-type activity	Homo sapiens
S146G	81% of wild-type activity	Homo sapiens
S146I	2.3% of wild-type activity	Homo sapiens
S147P	0.2% of wild-type activity	Homo sapiens
S165C	69.9% of wild-type activity	Homo sapiens
S262C	46.3% of wild-type activity	Homo sapiens
S28C	1.2% of wild-type activity	Homo sapiens
S28N	0.8 % of wild-type activity	Homo sapiens
S96F	1.0 % of wild-type activity	Homo sapiens
T145I	0.4% of wild-type activity	Homo sapiens
T145N	0.8% of wild-type activity	Homo sapiens
T58I	0.70% of wild-type activity	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P08397	-	-

Synonyms

Synonyms	Comment	Organism
HMBS	-	Homo sapiens