MSA check of two pseudo-enzyme claims

Reproducible alignment-level verification of catalytic-residue loss for two of the
pseudo-enzyme examples in the IBA_REVIEW findings (Pattern 7).
Earlier passes relied on UniProt CAUTION/FUNCTION text; this analysis independently
inspects the actual residues.

Run: uv run python catalytic_residue_msa.py (FAMSA alignment via pyfamsa).
Target sequences come from the repo's local genes/.../*-uniprot.txt; the reference
active enzyme (DPYS) and the catalytic-residue positions are pulled live from the
UniProt REST feature tables (with a documented hardcoded fallback for the AGO2
positions if the API returns none — not triggered in the runs reported here, which
used the live metal-binding-site features).

1. Human Argonautes AGO1–4 — RNase-H-like catalytic site (DDH of the DEDH tetrad)

Residues at the positions UniProt annotates on AGO2 as divalent-metal-binding
(the catalytic Asp/Asp/His — i.e. the DDH metal-coordinating subset of the
canonical DEDH slicer tetrad; the catalytic-glutamate "finger" is discussed in
the caveats and is not in the metal-binding feature set):

AGO2 position	AGO1	AGO2	AGO3	AGO4
D597	D	D	D	D
D669	D	D	D	G
H807	R	H	H	R

• AGO2 (the only human slicer) has the intact tetrad.
• AGO4 has two substitutions — D669G and H807R — consistent with no
  endonuclease activity. This is direct, alignment-level support for the AGO4 REMOVE
  (GO:0004521 RNA endonuclease activity).
• Nuance the MSA reveals: AGO3 retains the full tetrad (D/D/H), so its weak slicing
  is not explained by tetrad loss — a blanket "only AGO2 has the residues" would have
  been wrong. AGO1 loses only the catalytic His (H→R).

2. CRMP/DPYSL family vs active dihydropyrimidinase (DPYS, Q14117)

Residues at DPYS's UniProt-annotated Zn(2+)-coordinating / active-site positions:

DPYS position	DPYS	DPYSL2	DPYSL3	DPYSL4	DPYSL5	CRMP1
H67 (Zn)	H	H	H	H	S	N
H69 (Zn)	H	R	H	R	H	Y
K159 (carbamate→Zn)	K	L	M	L	Q	Q
H192 (Zn)	H	H	H	H	H	H
H248 (Zn)	H	K	K	K	N	K
D326 (Zn)	D	A	A	A	D	G

• All five CRMP/DPYSL paralogs have lost the carbamylated catalytic Lys159 — the
  residue that bridges the binuclear metal centre — plus several Zn-coordinating
  His/Asp. Without K159 there is no metal site and no amidohydrolase activity.
• This is first-hand confirmation of the UniProt CAUTION ("Lacks most of the conserved
  residues … essential for binding the metal cofactor") and supports the GO:0016812
  REMOVE across DPYSL2/3/4 (and the same basis for DPYSL5/CRMP1).

Caveats

• FAMSA with a UPGMA guide tree; results are robust because the inspected columns are
  deep, conserved active-site positions (unambiguous to align).
• UniProt annotated 3 metal-binding residues on AGO2 (the two Asp and the His that
  coordinate the cations); the "E" of the DEDH shorthand is the catalytic glutamate
  finger and is not in the metal-binding feature set, so it is not shown here.
• This verifies catalytic-residue loss, which is necessary (not by itself sufficient)
  evidence; it is corroborated by the experimental/curated statements cited in the
  findings.